Continued Exploration of Trifunctional Alkyl 4-Chloro-2-diazo-3-oxobutanoates: Streamlined Entry into [1,2,3]Triazolo[5,1- c ][1,4]benzoxazines and [1,2,3]Triazolo[5,1- c ][1,4]benzoxazepines

Article abstract of DOI:10.1055/a-1348-9031

Further exploration of the trifunctional character of previously introduced alkyl 4-chloro-2-diazo-3-oxobutanoates in reactions with N -protected substituted o -aminophenols followed by deprotection provided a convenient entry into [1,2,3]triazolo[5,1- c ][1,4]benzoxazines, which are of high medicinal importance, as documented in the literature. The same approach applied to N -protected substituted o -(aminomethyl)phenols afforded [1,2,3]triazolo[5,1- c ][1,4]benzoxazepines, which are practically unexplored compounds from a medicinal chemistry perspective. The syntheses start with S N 2-type alkylation of the phenol. Removal of the protecting group triggers imine formation followed by Wolff 1,2,3-triazole synthesis.

Full text of DOI:10.1055/a-1348-9031

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–L
paper
A
en
A. V. Budeev et al.
Paper
Synthesis
Continued Exploration of Trifunctional Alkyl 4-Chloro-2-diazo-3-
oxobutanoates: Streamlined Entry into [1,2,3]Triazolo[5,1-c][1,4]-
benzoxazines and [1,2,3]Triazolo[5,1-c][1,4]benzoxazepines
Anton V. Budeeva
Grigory Kantina
Dmitry Dar’in*a
Mikhail Krasavin*a,b
imine
formation
NHBoc
R3
NHBoc
OH
OH
0
0
0
0
-
0
0
0
2
-
0
4
1
3-7
4
1
3
R
O
OR
N
N
1)
1)
R3
/base (SN2)
/base (SN2)
0
0
0
0
-
0
0
0
2
-0
2
0
0
-
4
7
7
2
N
N
R
Cl
N
O
N
O
O
2) TFA, DCM, r.t., 18 h
3) AcONa, MeOH
45 °C, 22.5 h
2) TFA, DCM, r.t., 18 h
R'
N2
CO2R2
R1
a Saint Petersburg State University,
Saint Petersburg, 199034, Russian Federation
d.dariin@spbu.ru
CO2Et
SN
2
Wolff
triazole
synthesis
5 examples
69–79%
7 examples
47–91%
m.krasavin@spbu.ru
b Immanuel Kant Baltic Federal University,
Kaliningrad 236016, Russian Federation
DMSeMamiiknaihtiClraPoydmielr.Ddtr.Kkeearrsraasp’isbisonaaunv@vridignsnipnS@bgtsaupAt.erbuuutUh.nrouirvsersity, Saint Petersburg, 199034, Russian Federation
Received: 12.11.2020
Accepted: 08.01.2021
Published online: 08.01.2021
DOI: 10.1055/a-1348-9031; Art ID: ss-2020-z0584-op
with nucleophile-bearing primary amines to furnish fused
1,2,3-triazoles via a tandem of bimolecular nucleophilic
substitution, imine formation, and the Wolff 1,2,3-triazole
synthesis. This was demonstrated in reactions with vicinal
N,S-bis-nucleophiles and led to the formation of bicyclic
6,7-dihydro-4H-[1,2,3]triazolo[5,1-c][1,4]thiazines 2.5 These
reactions proceeded with good to excellent yields (67–96%),
and no fragmentation of the -oxo--diazocetate moiety
(known to be triggered by nucleophilic primary amines6)
was observed. Encouraged by this initial success, we were
keen to extend this methodology to other bis-nucleophilic
partners such as phenols bearing an amino functionality (in
a protected form to ensure the selectivity of the initial SN2
event7) attached to the ortho position of the phenyl ring, ei-
ther directly or via a 1–2 carbon linker. This was seen as a
potentially streamlined entry into 1,2,3-triazolo-fused tri-
cycles 3 featuring a variably sized oxa-ring (Scheme 1).
Herein, we report on the realization of this strategy.
Abstract Further exploration of the trifunctional character of previ-
ously introduced alkyl 4-chloro-2-diazo-3-oxobutanoates in reactions
with N-protected substituted o-aminophenols followed by deprotection
provided a convenient entry into [1,2,3]triazolo[5,1-c][1,4]benzox-
azines, which are of high medicinal importance, as documented in the
literature. The same approach applied to N-protected substituted
o-(aminomethyl)phenols afforded [1,2,3]triazolo[5,1-c][1,4]benzoxaze-
pines, which are practically unexplored compounds from a medicinal
chemistry perspective. The syntheses start with SN2-type alkylation of
the phenol. Removal of the protecting group triggers imine formation
followed by Wolff 1,2,3-triazole synthesis.
Key words diazo compounds, multicenter reactions, nucleophilic sub-
stitution, domino reactions, Wolff 1,2,3-triazole synthesis, benzox-
azines, benzoxazepines
Similar to multicomponent reactions, which are known
for their efficiency, the engagement of multiple reactive
centers in reagents participating in a two-component
transformation allows molecular complexity to be built up
rapidly and in atom-economical fashion.1 Ring-forming
processes based on one bifunctional reagent reacting with
another are rather common. Such reactions typically in-
volve the formation of two new chemical bonds via an ini-
tial intermolecular event followed by intramolecular ring
closure.2 In contrast, reagents with multiple reactive cen-
ters that can generate more than two new chemical bonds
through a domino process3 are much less widespread.4
Recently, we introduced trifunctional 4-chloro-2-diazo-
3-oxobutanoates 1a,b, which are capable of interacting
o-Aminophenols (and other phenols investigated in this
work) could not be directly used in the reactions with 1a,b
because, under basic conditions (required to activate the
phenolic substrates), the -dicarbonyl diazo reagents un-
dergo deacetylative fragmentation, as was observed previ-
ously.5 o-Aminophenol and its p-substituted derivatives
were Boc-protected by using a literature procedure,8 and
the resulting products 4a–e were obtained in excellent
yields. Doubly protected product 4f was synthesized from
2,4-diaminophenol dihydrochloride by using sodium bicar-
bonate as a base. Carboxamide 4g was obtained from car-
boxylic acid 4e by amidation. Boc-protected o-hydroxyben-
zylamines 5a–e were synthesized by reductive amination of
the respective benzaldehydes with tert-butyl carbamate by
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
A. V. Budeev et al.
Paper
Synthesis
Wolff
triazole
R'
N2
SN2
R'
N2
R'
CO2R
N
RO2C
synthesis
CO2R
R'
Nu
NH2
Nu
CO2R
N
N
Cl
Nu
(a)
N
O
O
N
N
Nu
SN2
NH2
1a, R = Et, R' = H
1b, R = R' = Me
imine
formation
HS
NH2
O
OR
O
N
X
N
N
Cl
X
(b)
S
CO2R
R'
N2
AcONa
MeOH, r.t., 16 h
R'
1a,b
2
NHPG
n
O
OR
N
N
N
n
Cl
1)
, base
OH
(c)
O
2) deprotection
CO2R
R'
1a,b
N2
O
3
Scheme 1 (a) Interaction of trifunctional reagents 1a,b with nucleophile-bearing primary amines; (b) tandem assembly of 6,7-dihydro-4H-[1,2,3]tri-
azolo[5,1-c][1,4]thiazines 2 reported previously;5 (c) approach to tricycles 3 explored in this work
R
NH2
OH
R
NHBoc
OH
Boc2O, Amberlyst-15
EtOH, r.t., overnight
using triethylsilane as the reducing agent.9 Finally, Boc-pro-
tected o-hydroxyphenethylamine (6) was synthesized in
two steps from 2-(2-nitrovinyl)phenol as described in the
literature (Scheme 2).10,11
For the suitably protected phenols 4a–d,f,g, 5a–e, and 6,
initial SN2-type coupling with trifunctional reagents 1a,b
was envisioned as the next step. After brief experimenta-
tion involving variation of the solvent, base, reaction tem-
perature, and additives, we arrived at an optimal protocol
that allowed alkylation of all of the above phenols in fair to
good yields (Table 1).
Not unexpectedly, alkylation of Boc-protected o-amino-
phenols 4a–d,f,g was generally higher yielding and pro-
ceeded over a shorter period of time than that of benzyl-
amines 5a–e and phenethylamine 6. Compound 1b was a
markedly less efficient alkylator than 1a (cf. entries 4 and 7,
Table 1).
With compounds 7a–g, 8a–e, and 9 in hand, we pro-
ceeded to remove the Boc protecting group; we reasoned
that this would liberate the primary amine and trigger the
tandem imine formation and the subsequent Wolff 1,2,3-
triazole synthesis (Scheme 1a). Indeed, for o-aminophenol-
derived substrates 7a–g, treatment with 10 equiv. of TFA in
DCM at room temperature over 18 h resulted in removal of
the Boc group and formation of [1,2,3]triazolo[5,1-c]-
[1,4]benzoxazines 10a–g in good to excellent yields
(Scheme 3).
4a, R = H, quant.
4b, R = Me, 65%
4c, R = t-Bu, 94%
4d, R = Cl, 72%
O
NH
4e, R = CO2H, 79%
N
4g, R =
EDC.HCl
HOBt, Et3N
DCM, r.t., 18 h
45%
BocHN
NHBoc
OH
Boc2O (2.2 equiv.)
H2N
NH2
OH
NaHCO3
aq. THF, r.t., 48 h
.2HCl
4f, 68%
BocNH2, Et3SiH, TFA
MeCN, r.t., 18 h
NHBoc
O
R
R
OH
OH
5a–e, 77–85%
(see experimental section)
NO2
NHBoc
1. LiAlH4
2. Boc2O, Et3N
OH
OH
6, 52%
Scheme 2 Preparation of starting phenols 4a–d,f,g, 5a–e, and 6;
HOBt: 1-hydroxy-1H-benzotriazole
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

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A. V. Budeev et al.
Paper
Synthesis
Table 1 Alkylation of Phenols 4a–d,f,g, 5a–e, and 6
NHBoc
O
O
n
Cl
CO2R2
N2
NHBoc
CO2R2
K2CO3, 18-crown-6, KI
MeCN, r.t.
O
n
R3
+
R1
1a,b
OH
R1
N2
R3
7a–g (n = 0)
8a–e (n = 1)
9 (n = 2)
4a–d,f,g (n = 0)
5a–e (n = 1)
6 (n = 2)
Entry
1
Phenol
1
Time (h)
6
Product
Yield (%)
75
NHBoc
O
O
CO2Et
4a
1a
7a
N2
NHBoc
O
O
CO2Et
2
3
4
5
4b
4c
4d
4f
1a
1a
1a
1a
6
6
6
6
7b
7c
7d
7e
79
75
83
73
N2
Me
tBu
Cl
NHBoc
O
O
CO2Et
N2
NHBoc
O
O
CO2Et
N2
O
NHBoc
O
CO2Et
N2
O
BocHN
NHBoc
O
CO2Et
6
4g
1a
31
7f
42
N
N2
O
NHBoc
O
O
CO2Me
7
8
4d
5a
1b
1a
51
24
7g
8a
40
58
Me
N2
Cl
NHBoc
O
O
CO2Et
CO2Et
N2
NHBoc
O
O
9
5b
5c
1a
1a
24
24
8b
8c
54
72
N2
OMe
NHBoc
O
O
CO2Et
10
N2
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

D
A. V. Budeev et al.
Paper
Synthesis
Table (continued)
Entry
Phenol
1
Time (h)
Product
Yield (%)
65
NHBoc
O
O
CO2Et
11
5d
5e
1a
1a
15
15
8d
N2
Cl
NHBoc
O
O
CO2Et
12a
8e
41
53
N2
O2N
NHBoc
O
13
6
1a
15.5
9
O
CO2Et
N2
a An equal volume of DMF was added to aid solubility of 5e.
The medicinal relevance of the [1,2,3]triazolo[5,1-
c][1,4]benzoxazine scaffold (typically assembled via an in-
tramolecular azide–alkyne click reaction12) is undisputable.
For example, this core is central to Glaxo’s 5-HT1A/B/D antag-
onists13 and mGluR5 receptor antagonists,14 developed as
antidepressants/anxyolytics, Shionogi’s HIV replication in-
hibitors15 and Takeda’s thrombin receptor antagonists.16
Under the same conditions that proved efficient in af-
fording 10a–g, removal of the Boc protecting group from
benzylamines 8a–e liberated a more basic alkylamino func-
tionality that was strongly protonated by TFA, which did
not allow the reaction to proceed further. This problem was
solved by neutralizing the TFA with sodium acetate (added
as a solution in methanol); this led, at elevated temperature,
to a slow and gradual formation of the expected [1,2,3]tri-
azolo[5,1-c][1,4]benzoxazepines 11a–e, which were isolat-
ed in good yields (Scheme 4).
R3
NHBoc
O
O
CO2R2
N
TFA
N
N
O
R1
N2
DCM
r.t.,18 h
R3
CO2R2
10a–g
R1
7a–g
Me
Cl
tBu
N
N
N
N
N
N
N
N
N
N
N
N
O
O
O
O
CO2Et
NH2
CO2Et
CO2Et
CO2Et
10c, 87%
10a, 83%
10d, 84%
10b, 91%
Cl
O
N
O
N
N
N
N
N
N
N
N
O
N
O
CO2Et
CO2Me
Me
CO2Et
10e, 47%
10g, 89%
10f, 60%
Scheme 3 Synthesis of [1,2,3]triazolo[5,1-c][1,4]benzoxazines 10a–g
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

E
A. V. Budeev et al.
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Synthesis
in the slow, high-yielding formation of [1,2,3]triazolo[5,1-
c][1,4]benzoxazepines, a much scarcer ring system that re-
mains to be studied with respect to biological activity. Al-
though the approach was found to be unsuitable for the
construction of the benzo[g][1,2,3]triazolo[5,1-c][1,4]oxaz-
ocine ring system, these findings significantly expand the
scope of cascade transformations achievable with the aid of
trifunctional alkyl 4-chloro-2-diazo-3-oxobutanoates.
NHBoc
O
R
O
1. TFA, DCM
r.t., 18 h
N
CO2Et
N
N
2. AcONa, MeOH
45 °C, 22.5 h
O
N2
R
CO2Et
8a–e
11a–e
N
N
N
N
N
N
N
N
N
MeO
O
O
O
CO2Et
CO2Et
CO2Et
All commercial reagents and solvents were used without further pu-
rification, unless otherwise noted. NMR spectroscopic data were re-
corded with a 400 MHz spectrometer (400.13 MHz for 1H and 100.61
MHz for 13C) in CDCl3 and in DMSO-d6 and were referenced to residual
solvent proton signals (H = 7.26 and H = 2.50, respectively) and sol-
vent carbon signals (C = 77.0 and C = 39.5, respectively). All chemical
shifts are reported in parts per million (ppm). Abbreviations used in
the description of resonances are: s (singlet), d (doublet), t (triplet), q
(quartet), br (broad), and m (multiplet). Coupling constants (J) are
quoted to the nearest 0.1 Hz. Mass spectra were recorded with a
HRMS-ESI-qTOF spectrometer (electrospray ionization mode). Melt-
ing points were determined with a Stuart SMP 50 melting point appa-
ratus in open capillary tubes. Analytical thin-layer chromatography
was performed on UV-254 silica gel plates with appropriate eluents.
Compounds were visualized with short-wavelength UV light. Flash
column chromatography was performed by using silica gel Merck
grade 60 (0.040−0.063 mm) 230−400 mesh (isocratic or gradient elu-
tion as indicated).
11b, 73%
11a, 69%
Cl
11c, 79%
O2N
N
N
N
N
N
N
O
O
CO2Et
CO2Et
11d, 76%
11e, 69%
Scheme 4 Synthesis of [1,2,3]triazolo[5,1-c][1,4]benzoxazepines 11a–e
The [1,2,3]triazolo[5,1-c][1,4]benzoxazepine scaffold is
a lot scarcer than [1,2,3]triazolo[5,1-c][1,4]benzoxazines. It
has only sporadically appeared in the literature,17 and
therefore, little is known of the associated biological activi-
ty, except for hints of a weak antibacterial and antifungal
activity.17d
Unfortunately, all attempts to assemble a homologous
ring system by exposing compound 9 to the same condi-
tions failed, even with a reaction time of several days. This
is possibly a result of unfavorable entropy associated with
the formation of an eight-membered ring (Scheme 5).18
Preparation of Starting Materials
tert-Butyl carbamate,19 2-(2-nitrovinyl)phenol,20 ethyl 4-chloro-2-di-
azo-3-oxobutanoate (1a), and methyl 4-chloro-2-diazo-3-oxopenta-
noate (1b)5 were prepared according to literature procedures. Data for
the obtained compounds were in accordance with the literature data.
N-Boc-Protected 2-Aminophenols 4a–e; General Procedure 1
NHBoc
(GP1)8
1. TFA, DCM
r.t., 18 h
N
N
O
The appropriate aminophenol (6.1 mmol) was added to a stirred mix-
ture of Amberlyst-15 (10% w/w) and di-tert-butyl dicarbonate (1.45 g,
6.7 mmol) in ethanol (6 mL) at room temperature. Stirring was con-
tinued overnight. After completion of the reaction, the catalyst was
filtered off and the solvent was evaporated in vacuo. The residue was
dissolved in CHCl3 (30 mL) and washed with water (3 × 30 mL). The
organic phase was dried over Na2SO4, filtered, and evaporated to dry-
ness to afford the corresponding N-Boc-protected 2-aminophenol.
N
O
CO2Et
2. AcONa, MeOH
45 °C
up to 7 d
O
CO2Et
N2
9
0%
Scheme 5 Attempted assembly of the benzo[g][1,2,3]triazolo[5,1-c]-
[1,4]oxazocine ring system
The spectral data for tert-butyl (2-hydroxyphenyl)carbamate (4a)
(1.91 g, quant.),21 tert-butyl (2-hydroxy-5-methylphenyl)carbamate
(4b) (1.71 g, 65%),22 and tert-butyl (5-chloro-2-hydroxyphenyl)carba-
mate (4d) (1.77 g, 72%)21 thus obtained were in accordance with the
literature data.
In summary, we have extended the trifunctional reac-
tivity of the previously reported alkyl 4-chloro-2-diazo-3-
oxobutanoates to O,N-bis-nucleophilic substrates. These
were engaged in ring-forming processes, in N-Boc-protect-
ed form, in two steps. Initially, SN2-type displacement of
the chlorine atom generated phenoxy-substituted precur-
sors that were isolated. Removal of the Boc protecting
group with TFA from anilinic substrates triggered cascade
imine formation and Wolff 1,2,3-triazole synthesis. This af-
forded [1,2,3]triazolo[5,1-c][1,4]benzoxazines, which are
well characterized from a medicinal chemistry perspective.
Deprotection of the more basic benzylamines required the
TFA salt to be neutralized by sodium acetate. This resulted
tert-Butyl (5-(tert-Butyl)-2-hydroxyphenyl)carbamate (4с)
Following GP1, 2-amino-4-(tert-butyl)phenol (1 g, 6.1 mmol), Boc2O
(1.45 g, 6.7 mmol), and Amberlyst-15 (100 mg) in ethanol (6 mL) gave
tert-butyl (5-(tert-butyl)-2-hydroxyphenyl)carbamate (4c) as a light
brown solid (1.51 g, 94%); mp 102.5–103.6 °С.
1H NMR (400 MHz, CDCl3):  = 8.14 (br s, 1 H, NH), 7.13–7.01 (m, 2 H),
6.93 (d, J = 8.5 Hz, 1 H, 3-Ar), 6.68 (br s, 1 H, OH), 1.55 (s, 9 H, C(CH3)3
(Boc)), 1.30 (s, 9 H, C(CH3)3 (tBu-Ph)).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

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A. V. Budeev et al.
Paper
Synthesis
13C NMR (101 MHz, CDCl3):  = 155.22, 145.39, 143.79, 124.66,
122.85, 118.77, 118.66, 82.03, 34.07, 31.46 (3 C, C(CH3)3), 28.28 (3 C,
C(CH3)3).
13C NMR (101 MHz, DMSO-d6):  = 168.60, 153.28, 149.02, 128.24,
126.26, 123.46, 120.63, 114.71, 79.86, 49.66, 46.48, 28.50 (3 C,
C(CH3)3), 26.53, 24.37.
HRMS (ESI +ve): m/z calcd for C15H23NO3 [M + Na]+: 288.1570; found:
HRMS (ESI +ve): m/z calcd for C16H22N2O4 [M + Na]+: 329.1472; found:
288.1571.
329.1472.
3-((tert-Butoxycarbonyl)amino)-4-hydroxybenzoic acid (4e)
tert-Butyl (2-Hydroxybenzyl)carbamates 5a–e; General Procedure
2 (GP2)9
Following GP1, 3-amino-4-hydroxybenzoic acid (1.0 g, 6.3 mmol),
Boc2O (1.57 g, 7 mmol), and Amberlyst-15 (100 mg) in ethanol (6.5
mL) were used. In this case, flash chromatography was performed (ac-
etone as the eluent), which gave 3-((tert-butoxycarbonyl)amino)-4-
hydroxybenzoic acid (4e) as a colorless solid (1.27 g, 79%); mp 168.7–
169.7 °С.
1H NMR (400 MHz, DMSO-d6):  = 12.45 (br s, 1 H, COOH), 10.62 (br s,
1 H, OH), 8.28 (d, J = 2.0 Hz, 1 H, 2-Ar), 7.87 (s, 1 H, NH), 7.52 (dd, J =
8.4, 2.2 Hz, 1 H, 6-Ar), 6.89 (d, J = 8.4 Hz, 1 H, 5-Ar), 1.47 (s, 9 H,
C(CH3)3).
The appropriate salicylaldehyde (2.5 mmol), Et3SiH (1.198 mL, 7.34
mmol), and TFA (0.371 mL, 4.85 mmol) were added to a solution of
tert-butylcarbamate (852 mg, 7.27 mmol) in CH3CN (11 mL), and the
reaction mixture was stirred at room temperature for the indicated
time. Organic solvent was removed in vacuo, then the residue was
dissolved in DCM (15 mL) and washed with a sat. solution of NaHCO3
(2 × 20 mL) and brine (20 mL). The organic layer was dried over
Na2SO4, filtered, and concentrated under reduced pressure. The resi-
due was purified by column chromatography to obtain corresponding
tert-butyl (2-hydroxybenzyl)carbamate.
13C NMR (101 MHz, DMSO-d6):  = 167.66, 153.21, 151.92, 126.62,
126.03, 122.56, 121.90, 114.96, 79.89, 28.49 (3 C, C(CH3)3).
HRMS (ESI +ve): m/z calcd for C12H15NO5 [M + Na]+: 276.0842; found:
The data for tert-butyl (2-hydroxybenzyl)carbamate (5a) (359 mg,
65%) were in accordance with the literature data.24
276.0847.
tert-Butyl (2-Hydroxy-3-methoxybenzyl)carbamate (5b)
Following GP2, 2-hydroxy-3-methoxybenzaldehyde (380 mg, 2.5
mmol) and other reagents were used in the indicated quantities with
a reaction time of 20 h. Yield 532 mg (84%); colorless solid; mp 136.3–
136.9 °С.
1H NMR (400 MHz, CDCl3):  = 6.88–6.77 (m, 4 H, Ar and OH overlap-
ping), 5.16 (br s, 1 H, NH), 4.33 (d, J = 6.3 Hz, 2 H, ArCH2), 3.90 (s, 3 H,
OCH3), 1.46 (s, 9 H, C(CH3)3).
13C NMR (101 MHz, CDCl3):  = 156.68, 147.21, 144.19, 124.93,
121.84, 119.57, 110.47, 79.84, 56.05, 40.33 (ArCH2), 28.41 (3 C,
C(CH3)3).
Di-tert-butyl (4-Hydroxy-1,3-phenylene)dicarbamate (4f)
A solution of NaHCO3 (2.17 g, 25.9 mmol) in water (25 mL) was added
to a stirred solution of 2,4-diaminophenol dihydrochloride (1.00 g,
5.1 mmol) in THF (25 mL). Stirring was continued for 15 min at room
temperature, and Boc2O (2.33 g, 10.7 mmol) was added. The reaction
mixture was stirred for 48 h at room temperature. THF was removed
in vacuo, then the water was extracted with DCM (3 × 30 mL). The
organic layer was dried over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by column chromatogra-
phy to obtain di-tert-butyl (4-hydroxy-1,3-phenylene)dicarbamate
(4f) as a light lilac solid (1.11 g, 68%); mp 81.4–82.5 °С.
HRMS (ESI +ve): m/z calcd for C13H19NO4 [M + Na]+: 276.1206; found:
276.1208.
1H NMR (400 MHz, CDCl3):  = 7.88 (br s, 1 H), 7.41 (br s, 1 H), 6.89 (d,
J = 8.5 Hz, 1 H, 5-Ar), 6.83 (dd, J = 8.7, 2.5 Hz, 1 H, 6-Ar), 6.65 (br s, 1
H), 6.34 (br s, 1 H), 1.54 (s, 9 H, C(CH3)3), 1.52 (s, 9 H, C(CH3)3).
tert-Butyl ((2-Hydroxynaphthalen-1-yl)methyl)carbamate (5c)
13C NMR (101 MHz, CDCl3):  = 154.71, 153.39, 143.17, 131.17,
126.05, 118.57, 116.34, 112.52, 81.85, 80.50, 28.35 (3 C, C(CH3)3),
28.25 (3 C, C(CH3)3).
Following GP2, 2-hydroxy-1-naphthaldehyde (430 mg, 2.5 mmol) and
other reagents were used in the indicated quantities with a reaction
time of 3 d. Yield 578 mg (85%); beige solid; mp 140.2–140.9 °С.
HRMS (ESI +ve): m/z calcd for C16H24N2O5 [M + Na]+: 347.1577; found:
347.1579.
1H NMR (400 MHz, CDCl3):  = 9.57 (s, 1 H, OH), 7.82 (d, J = 8.3 Hz, 1 H,
Ar), 7.79 (d, J = 8.4 Hz, 1 H, Ar), 7.76 (d, J = 8.9 Hz, 1 H, Ar), 7.52 (ddd,
J = 8.3, 6.8, 1.4 Hz, 1 H, Ar), 7.36 (ddd, J = 8.0, 6.8, 1.1 Hz, 1 H, Ar), 7.26
(d, J = 8.9 Hz, 1 H, Ar), 5.47 (t, J = 6.8 Hz, 1 H, NH), 4.69 (d, J = 6.7 Hz, 2
H, ArCH2), 1.45 (s, 9 H, C(CH3)3).
tert-Butyl (2-Hydroxy-5-(pyrrolidine-1-carbonyl)phenyl)carba-
mate (4g)23
EDC?HCl (360 mg, 1.78 mmol), HOBt (301 mg, 1.78 mmol), Et3N (248
μL, 1.78 mmol), and pyrrolidine (147 μL, 1.78 mmol) were added to a
stirred solution of 3-((tert-butoxycarbonyl)amino)-4-hydroxybenzoic
acid (4e) (443 mg, 1.75 mmol) in DCM (10 mL). The reaction mixture
was stirred for 18 h at room temperature and then diluted with DCM
(20 mL). The reaction mixture was washed with water (2 × 15 mL) and
brine (15 mL). The organic layer was dried over Na2SO4, filtered, and
concentrated under reduced pressure. The residue was purified by
column chromatography to obtain tert-butyl (2-hydroxy-5-(pyrroli-
dine-1-carbonyl)phenyl)carbamate (4g) as a colorless solid (242 mg,
45%); mp 196.9–197.8 °С.
13C NMR (101 MHz, CDCl3):  = 158.79, 154.11, 133.00, 129.97,
129.08, 128.92, 126.80, 123.00, 121.22, 120.46, 116.67, 81.30, 35.54
(ArCH2), 28.31 (3 C, C(CH3)3).
HRMS (ESI +ve): m/z calcd for C16H19NO3 [M + Na]+: 296.1257; found:
296.1254.
tert-Butyl (5-Chloro-2-hydroxybenzyl)carbamate (5d)
Following GP2, 5-chloro-2-hydroxybenzaldehyde (390 mg, 2.5 mmol)
and other reagents were used in the indicated quantities with a reac-
tion time of 16 h. Yield 524 mg (82%); colorless solid; mp 133.3–134.0
°С.
1H NMR (400 MHz, DMSO-d6):  = 10.20 (s, 1 H, OH), 7.86–7.84 (m, 2
H, 6-Ar and NH overlapping), 7.09 (dd, J = 8.3, 2.1 Hz, 1 H, 4-Ar), 6.84
(d, J = 8.2 Hz, 1 H, 3-Ar), 3.49–3.39 (t, J = 6.4 Hz, 4 H, (CH2)2, pyrroli-
dine), 1.83 (br s, 4 H, (CH2)2, pyrrolidine), 1.47 (s, 9 H, C(CH3)3).
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A. V. Budeev et al.
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1H NMR (400 MHz, CDCl3):  = 9.06 (br s, 1 H, OH), 7.17 (dd, J = 8.6, 2.6
Hz, 1 H, 4-Ar), 7.05 (d, J = 2.6 Hz, 1 H, 6-Ar), 6.89 (d, J = 8.6 Hz, 1 H, 3-
Ar), 5.28 (br s, 1 H, NH), 4.20 (d, J = 6.7 Hz, 2 H, ArCH2), 1.47 (s, 9 H,
C(CH3)3).
HRMS (ESI +ve): m/z calcd for C13H19NO3 [M + Na]+: 260.1257; found:
260.1259.
Compounds 7a–g; General Procedure 3 (GP3)
13C NMR (101 MHz, CDCl3):  = 158.49, 154.48, 130.10, 129.52,
126.44, 124.22, 119.19, 81.60, 40.93 (ArCH2), 28.28 (3 C, C(CH3)3).
HRMS (ESI +ve): m/z calcd for C12H16ClNO3 [M + Na]+: 280.0711;
The appropriate N-Boc-protected aminophenol 4 (1.5 mmol), K2CO3
(311 mg, 2.25 mmol), and 18-crown-6 (40 mg, 0.15 mmol) were dis-
solved in HPLC-grade MeCN (6 mL) and stirred at room temperature
for 15 min. KI (25 mg, 0.15 mmol) and the appropriate 4-chloro-2-
diazo-3-oxobutanoate (as a solution in 1 mL of HPLC-grade CH3CN,
286 mg, 1.5 mmol) were added, and the reaction mixture was stirred
at room temperature for 6 h (TLC control). The organic solvent was
removed in vacuo. The residue was dissolved in DCM (10 mL) and
washed with H2O (2 × 15 mL) and brine (15 mL). The organic layer
was dried over Na2SO4, filtered, and concentrated under reduced pres-
sure. The residue was purified by column chromatography to obtain
the corresponding alkylation product.
found: 280.0708.
tert-Butyl (2-Hydroxy-5-nitrobenzyl)carbamate (5e)
Following GP2, 2-hydroxy-5-nitrobenzaldehyde (420 mg, 2.5 mmol)
and other reagents were used in the indicated quantities with a reac-
tion time of 26 h. After completion of the reaction, the mixture was
left to stand overnight in a freezer (–18 °C). The solid was isolated by
suction and carefully rinsed with DCM (2 × 5 mL) and CH3CN (4 mL).
Yield 516 mg (77%); colorless solid; mp 181.0–181.6 °С.
1H NMR (400 MHz, DMSO-d6):  = 11.21 (br s, 1 H, OH), 8.04 (dd, J =
8.8, 2.9 Hz, 1 H, 4-Ar), 8.00 (d, J = 2.9 Hz, 1 H, 6-Ar), 7.42 (t, J = 6.2 Hz,
1 H, NH), 6.97 (d, J = 8.9 Hz, 1 H, 3-Ar), 4.12 (d, J = 6.2 Hz, 2 H, ArCH2),
1.42 (s, 9 H, C(CH3)3).
13C NMR (101 MHz, DMSO-d6):  = 161.55, 156.42, 140.00, 127.91,
124.70, 123.55, 115.43, 78.61, 38.56 (ArCH2), 28.67 (3 C, C(CH3)3).
Ethyl 4-(2-((tert-Butoxycarbonyl)amino)phenoxy)-2-diazo-3-
oxobutanoate (7a)
Following GP3, tert-butyl (2-hydroxyphenyl)carbamate (4a) (320 mg,
1.53 mmol), ethyl 4-chloro-2-diazo-3-oxobutanoate (1a) (292 mg,
1.53 mmol), and other reagents in corresponding quantities were
used to give ethyl 4-(2-((tert-butoxycarbonyl)amino)phenoxy)-2-di-
azo-3-oxobutanoate (7a) as a yellowish solid (417 mg, 75%); mp
124.2–125.6 °C (decomp.).
HRMS (ESI +ve): m/z calcd for C12H16N2O5 [M + Na]+: 291.0951; found:
291.0949.
1H NMR (400 MHz, CDCl3):  = 8.11 (d, J = 8.1 Hz, 1 H, 3-Ar), 7.61 (br s,
1 H, NH), 7.00 (ddd, J = 7.9, 7.7, 1.5 Hz, 1 H, 5-Ar), 6.93 (ddd, J = 7.8,
7.6, 1.7 Hz, 1 H, 4-Ar), 6.82 (dd, J = 8.0, 1.5 Hz, 1 H, 6-Ar), 5.21 (s, 2 H,
OCH2C(O)), 4.36 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.55 (s, 9 H, C(CH3)3),
1.38 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.31, 161.08, 152.92, 146.64,
129.46, 122.62, 122.24, 118.98, 113.23, 80.19, 75.24 (C=N2), 72.84,
61.98, 28.39 (3 C, C(CH3)3), 14.32.
tert-Butyl (2-Hydroxyphenethyl)carbamate (6)10,11
LiAlH4 (366 mg, 9.65 mmol) was suspended in dry THF (3.5 mL) in a
25 mL round-bottom flask equipped with a pressure-equalizing drop-
ping funnel, a condenser, and a drying tube. A solution of 2-(2-nitro-
vinyl)phenol (486 mg, 2.92 mmol) in dry THF (7 mL) was added drop-
wise (over 1.5 h) to a stirred and cooled (0 °С) suspension of LiAlH4
(avoid boiling the solvent!). After completion of the dropwise addi-
tion, the reaction mixture was stirred for another 10 min at 0 °С, then
for 2 h at room temperature. The reaction mixture was cooled to 0 °С,
and then H2O (10 mL) was added. To this mixture, 10% HCl (20 mL)
was added and washed with EtOAc (2 × 10 mL). The combined organic
layers were extracted with 10% HCl (3 × 10 mL). The combined aque-
ous layers were treated with tartaric acid (4 equiv., 1770 mg), the pH
value was adjusted to 10 with concd. aq. NH3, and the aqueous layers
were extracted with CHCl3 (6 × 10 mL). The organic phase was dried
over Na2SO4. The solvent was removed under reduced pressure to af-
ford crude (2-hydroxyphenethyl)amine, which was used in the next
step without any purification. A solution of this crude material (257
mg), di-tert-butyldicarbonate (422 mg, 1.87 mmol), NEt3 (0.261 mL,
1.87 mmol) in H2O (1.9 mL), and THF (4.5 mL) was stirred overnight at
room temperature. The THF was then removed by rotary evaporation,
and the aqueous residue was extracted with ethyl acetate (3 × 8 mL).
The organic phase was dried over Na2SO4. The solvent was removed
under reduced pressure. The residue was purified by column chroma-
tography to obtain the title compound as a yellowish crystals (366
mg, 52%); mp 78.5–79.7 °С.
HRMS (ESI +ve): m/z calcd for C17H21N3O6 [M + Na]+: 386.1323; found:
386.1312.
Ethyl 4-(2-((tert-Butoxycarbonyl)amino)-4-methylphenoxy)-2-di-
azo-3-oxobutanoate (7b)
Following GP3, tert-butyl (2-hydroxy-5-methylphenyl)carbamate
(4b) (335 mg, 1.5 mmol), ethyl 4-chloro-2-diazo-3-oxobutanoate (1a)
(286 mg, 1.5 mmol), and other reagents in corresponding quantities
were used to give ethyl 4-(2-((tert-butoxycarbonyl)amino)phenoxy)-
2-diazo-3-oxobutanoate (7b) as a beige solid (449 mg, 79%); mp 98.3–
98.6 °C (decomp.).
1H NMR (400 MHz, CDCl3):  = 7.95 (br s, 1 H), 7.62 (br s, 1 H), 6.75–
6.70 (m, 2 H, 5-Ar and 6-Ar overlapping), 5.18 (s, 2 H, OCH2C(O)), 4.35
(q, J = 7.1 Hz, 2 H, OCH2CH3), 2.30 (s, 3 H, ArCH3), 1.55 (s, 9 H, C(CH3)3),
1.37 (t, J = 7.2 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.59, 161.08, 152.98, 144.68,
132.33, 129.18, 122.58, 119.54, 113.35, 80.12, 75.20 (C=N2), 73.21,
61.95, 28.39 (3 C, C(CH3)3), 21.07 (ArCH3), 14.32.
HRMS (ESI +ve): m/z calcd for C18H23N3O6 [M + Na]+: 400.1479; found:
400.1474.
1H NMR (400 MHz, CDCl3):  = 7.46 (br s, 1 H, OH), 7.14 (ddd, J = 7.66,
7.60, 1.51 Hz, 1 H, 4-Ar), 7.08 (dd, J = 7.5, 1.7 Hz, 1 H, 6-Ar), 6.89 (dd,
J = 7.95, 1.10 Hz, 1 H, 3-Ar), 6.84 (ddd, J = 7.43, 7.39, 1.08 Hz, 1 H, 5-
Ar), 4.98 (br s, 1 H, NH), 3.35 (q, J = 6.7 Hz, 2 H, ArCH2CH2), 2.86 (t, J =
7.1 Hz, 2 H, ArCH2CH2), 1.48 (s, 9 H, C(CH3)3).
13C NMR (101 MHz, CDCl3):  = 157.07, 155.00, 130.54, 127.97,
124.83, 120.07, 115.97, 80.08 (C(CH3)3), 40.96 (ArCH2CH2), 31.32
(ArCH2CH2), 28.41 (3 C, C(CH3)3).
Ethyl 4-(2-((tert-Butoxycarbonyl)amino)-4-(tert-butyl)phenoxy)-
2-diazo-3-oxobutanoate (7c)
Following GP3, tert-butyl (5-(tert-butyl)-2-hydroxyphenyl)carbamate
(4c) (400 mg, 1.5 mmol), ethyl 4-chloro-2-diazo-3-oxobutanoate (1a)
(286 mg, 1.5 mmol), and other reagents in corresponding quantities
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

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A. V. Budeev et al.
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were used to give ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-(tert-
butyl)phenoxy)-2-diazo-3-oxobutanoate (7c) as a beige solid (472
mg, 75%); mp 107.1–108.3 °C (decomp.).
1H NMR (400 MHz, CDCl3):  = 8.17 (br s, 1 H), 7.59 (br s, 1 H), 6.94
(dd, J = 8.5, 2.4 Hz, 1 H, 5-Ar), 6.74 (d, J = 8.5 Hz, 1 H, 6-Ar), 5.19 (s, 2
H, OCH2C(O)), 4.35 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.56 (s, 9 H, C(CH3)3
(Boc)), 1.37 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.33 (s, 9 H, C(CH3)3 (tBu-
Ph)).
1H NMR (400 MHz, CDCl3):  = 8.33 (br s, 1 H), 7.55 (br s, 1 H), 7.19
(dd, J = 8.4, 2.1 Hz, 1 H, 5-Ar), 6.81 (d, J = 8.4 Hz, 1 H, 6-Ar), 5.24 (s, 2
H, OCH2C(O)), 4.37 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.57 (dt, J = 42.0, 6.6
Hz, 4 H, pyrrolidine), 2.00–1.84 (m, 4 H, pyrrolidine), 1.55 (s, 9 H,
C(CH3)3), 1.39 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 186.79, 169.26, 161.04, 152.70,
147.38, 131.31, 128.70, 121.93, 117.75, 112.59, 80.45, 75.32 (C=N2),
72.44, 62.06, 28.37 (3 C, C(CH3)3), 14.33.
13C NMR (101 MHz, CDCl3):  = 187.61, 161.08, 152.93, 145.62,
144.55, 128.90, 118.87, 116.54, 112.82, 79.99, 75.21 (C=N2), 73.09,
61.95, 34.51, 31.50 (3 C, C(CH3)3), 28.45 (3 C, C(CH3)3), 14.33.
HRMS (ESI +ve): m/z calcd for C22H28N4O7 [M + Na]+: 483.1850; found:
483.1862.
HRMS (ESI +ve): m/z calcd for C21H29N3O6 [M + Na]+: 442.1949; found:
Methyl 4-(2-((tert-Butoxycarbonyl)amino)-4-chlorophenoxy)-2-
diazo-3-oxopentanoate (7g)
442.1947.
Following GP3, tert-butyl (5-chloro-2-hydroxyphenyl)carbamate (4d)
(300 mg, 1.23 mmol), K2CO3 (255 mg, 1.85 mmol), 18-crown-6 (33
mg, 0.12 mmol), KI (20 mg, 0.12 mmol), and methyl 4-chloro-2-di-
azo-3-oxopentanoate 1b (235 mg, 1.23 mmol) were used in HPLC-
grade CH3CN (3 mL). In this case, the reaction temperature was 30 °С
and the reaction time was 51 h. Yield 198 mg (40%); beige solid; mp
115.4–116.2 °С (decomp.).
1H NMR (400 MHz, CDCl3):  = 8.17 (br s, 1 H), 7.55 (br s, 1 H), 6.85
(dd, J = 8.6, 2.6 Hz, 1 H, 5-Ar), 6.69 (d, J = 8.7 Hz, 1 H, 6-Ar), 5.76 (q, J =
6.7 Hz, 1 H, CHCH3), 3.89 (s, 3 H, OCH3), 1.63 (d, J = 6.7 Hz, 3 H,
CHCH3), 1.56 (s, 9 H, C(CH3)3).
13C NMR (101 MHz, CDCl3):  = 190.72, 161.07, 152.57, 144.32,
130.59, 127.74, 121.71, 118.86, 114.58, 80.71, 77.17 (CHCH3), 75.54
(C=N2), 52.58, 28.34 (3 C, C(CH3)3) 18.17 (СHCH3).
HRMS (ESI +ve): m/z calcd for C17H20ClN3O6 [M + Na]+: 420.0933;
found: 420.0943.
Ethyl 4-(2-((tert-Butoxycarbonyl)amino)-4-chlorophenoxy)-2-di-
azo-3-oxobutanoate (7d)
Following GP3, tert-butyl (5-chloro-2-hydroxyphenyl)carbamate (4d)
(370 mg, 1.5 mmol), ethyl 4-chloro-2-diazo-3-oxobutanoate (1a)
(286 mg, 1.5 mmol), and other reagents in corresponding quantities
were used to give ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-(tert-
butyl)phenoxy)-2-diazo-3-oxobutanoate (7d) as a beige solid (502
mg, 83%); mp 87.4–88.1 °C (decomp.).
1H NMR (400 MHz, CDCl3):  = 8.20 (br s, 1 H), 7.61 (br s, 1 H), 6.89
(dd, J = 8.6, 2.5 Hz, 1 H, 5-Ar), 6.73 (d, J = 8.7 Hz, 1 H, 6-Ar), 5.20 (s, 2
H, OCH2C(O)), 4.36 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.56 (s, 9 H, C(CH3)3),
1.38 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.00, 161.02, 152.56, 145.12,
130.52, 127.88, 121.71, 118.81, 114.09, 80.71, 75.27 (C=N2), 72.99,
62.05, 28.33 (3 C, C(CH3)3), 14.33.
HRMS (ESI +ve): m/z calcd for C17H20ClN3O6 [M + Na]+: 420.0933;
found: 420.0929.
Compounds 8a–e and 9; General Procedure 4 (GP4)
The appropriate N-Boc-protected salicylamine (0.63 mmol), K2CO3
(131 mg, 0.95 mmol), and 18-crown-6 (17 mg, 0.064 mmol) were dis-
solved in HPLC-grade CH3CN (2 mL) and stirred at room temperature
for 15 min. KI (11 mg, 0.066 mmol) and ethyl 4-chloro-2-diazo-3-
oxobutanoate (as a solution in 1 mL of HPLC-grade CH3CN, 145 mg,
0.76 mmol) were added, and the reaction mixture was stirred at room
temperature for the indicated time (TLC control). The organic solvent
was removed in vacuo. The residue was dissolved in DCM (15 mL) and
washed with H2O (2 × 10 mL) and brine (10 mL). The organic layer
was dried over Na2SO4, filtered, and concentrated under reduced pres-
sure. The residue was purified by column chromatography to obtain
the corresponding alkylation product.
Ethyl 4-(2,4-Bis((tert-butoxycarbonyl)amino)phenoxy)-2-diazo-3-
oxobutanoate (7e)
Following GP3, di-tert-butyl (4-hydroxy-1,3-phenylene)dicarbamate
(4f) (490 mg, 1.5 mmol), ethyl 4-chloro-2-diazo-3-oxobutanoate (1a)
(286 mg, 1.5 mmol), and other reagents in corresponding quantities
were used to give ethyl 4-(2,4-bis((tert-butoxycarbonyl)amino)phen-
oxy)-2-diazo-3-oxobutanoate (7e) as a colorless solid (526 mg, 73%);
mp 157.9–158.4 °C (decomp.).
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 2.6 Hz, 1 H, 3-Ar), 7.69 (br s,
1 H), 7.24 (br s, 1 H), 6.78 (d, J = 8.8 Hz, 1 H, 6-Ar), 6.40 (br s, 1 H), 5.17
(s, 2 H, OCH2C(O)), 4.35 (q, J = 7.2 Hz, 2 H, OCH2CH3), 1.54 (s, 9 H,
C(CH3)3), 1.51 (s, 9 H, C(CH3)3), 1.37 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.62, 161.05, 152.96, 152.82,
142.73, 133.35, 129.95, 114.36, 112.69, 109.93, 80.36, 80.20, 75.24
(C=N2), 73.60, 61.98, 28.36 (3 C, C(CH3)3), 28.34 (3 C, C(CH3)3), 14.32.
HRMS (ESI +ve): m/z calcd for C22H30N4O8 [M + Na]+: 501.1956; found:
501.1968.
Ethyl 4-(2-(((tert-Butoxycarbonyl)amino)methyl)phenoxy)-2-di-
azo-3-oxobutanoate (8a)
Following GP4, tert-butyl (2-hydroxybenzyl)carbamate (5a) (140 mg,
0.63 mmol) and other reagents were used in the indicated quantities
with a reaction time of 24 h. Yield 138 mg (58%); colorless solid; mp
60.4–61.6 °C.
1H NMR (400 MHz, CDCl3):  = 7.33 (d, J = 7.5 Hz, 1 H, 3-Ar), 7.22 (ddd,
J = 7.86, 7.80, 1.74 Hz, 1 H, 5-Ar), 6.96 (ddd, J = 7.46, 7.44, 1.07 Hz, 1 H,
4-Ar), 6.79 (dd, J = 8.2, 0.9 Hz, 1 H, 6-Ar), 5.67 (br s, 1 H, NH), 5.22 (s, 2
H, OCH2C(O)), 4.45–4.30 (m, 4 H, ArCH2 and OCH2CH3 overlapping),
1.46 (s, 9 H, C(CH3)3), 1.39 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.13, 161.13, 156.17, 156.09,
130.06, 128.54, 128.02, 121.67, 111.57, 78.94, 75.31 (C=N2), 71.02,
61.95, 40.72 (ArCH2), 28.47 (3 C, C(CH3)3), 14.33.
Ethyl4-(2-((tert-Butoxycarbonyl)amino)-4-(pyrrolidine-1-carbon-
yl)phenoxy)-2-diazo-3-oxobutanoate (7f)
Following GP3, tert-butyl (2-hydroxy-5-(pyrrolidine-1-carbonyl)phe-
nyl)carbamate (4g) (150 mg, 0.49 mmol), K2CO3 (135 mg, 0.98 mmol),
18-crown-6 (13 mg, 0.05 mmol), KI (8 mg, 0.05 mmol), and ethyl 4-
chloro-2-diazo-3-oxobutanoate (1a) (140 mg, 0.73 mmol) were used
in HPLC-grade CH3CN (5 mL) for a reaction time of 31 h. Yield 94 mg
(42%); brownish wax; mp 106.8–107.6 °С (decomp.).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

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A. V. Budeev et al.
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HRMS (ESI +ve): m/z calcd for C18H23N3O6 [M + H]+: 378.1660; found:
Ethyl 4-(2-(((tert-Butoxycarbonyl)amino)methyl)-4-nitrophen-
378.1660.
oxy)-2-diazo-3-oxobutanoate (8e)
Following GP4, tert-butyl (2-hydroxy-5-nitrobenzyl)carbamate (5e)
(170 mg, 0.63 mmol) and other reagents were used in the indicated
quantities. In this case, because of the poor solubility of 5e in CH3CN,
the reaction was performed in a mixture of CH3CN (1.5 mL) and dry
DMF (1.5 mL). The reaction time was 15 h. Yield 110 mg (41%);
brownish solid; mp 97.7–98.4 °C (decomp.).
1H NMR (400 MHz, CDCl3):  = 8.23 (d, J = 2.8 Hz, 1 H, 3-Ar), 8.15 (dd,
J = 9.0, 2.8 Hz, 1 H, 5-Ar), 6.81 (d, J = 9.1 Hz, 1 H, 6-Ar), 5.42 (br s, 1 H,
NH), 5.32 (s, 2 H, OCH2C(O)), 4.46 (d, J = 6.2 Hz, 2 H, ArCH2), 4.39 (q, J =
7.1 Hz, 2 H, OCH2CH3), 1.48 (s, 9 H, C(CH3)3), 1.40 (t, J = 7.1 Hz, 3 H,
OCH2CH3).
Ethyl 4-(2-(((tert-Butoxycarbonyl)amino)methyl)-6-methoxyphen-
oxy)-2-diazo-3-oxobutanoate (8b)
Following GP4, tert-butyl (2-hydroxy-3-methoxybenzyl)carbamate
(5b) (160 mg, 0.63 mmol) and other reagents were used in the indi-
cated quantities with a reaction time of 24 h. Yield 138 mg (54%); pale
green oil.
1H NMR (400 MHz, CDCl3):  = 7.02 (dd, J = 7.91, 7.82 Hz, 1 H, 4-Ar),
6.96 (d, J = 7.5 Hz, 1 H, Ar), 6.85 (dd, J = 8.1, 1.7 Hz, 1 H, Ar), 5.65 (br s,
1 H, NH), 5.25 (s, 2 H, OCH2C(O)), 4.41 (d, J = 6.2 Hz, 2 H, ArCH2), 4.32
(q, J = 7.2 Hz, 2 H, OCH2CH3), 3.86 (s, 3 H, OCH3), 1.45 (s, 9 H, C(CH3)3),
1.36 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 185.64, 161.03, 160.70, 155.93,
141.92, 129.30, 124.69 (2 С), 111.12, 79.70, 75.49 (C=N2), 71.16, 62.18,
40.01 (ArCH2), 28.39 (3 C, C(CH3)3), 14.34.
13C NMR (101 MHz, CDCl3):  = 188.46, 161.10, 156.10, 151.64,
145.76, 132.83, 124.07, 121.77, 111.93, 78.99, 75.25, 75.07 (C=N2),
61.75, 55.90, 40.57 (ArCH2), 28.44 (3 C, C(CH3)3), 14.31.
HRMS (ESI +ve): m/z calcd for C18H22N4O8 [M + Na]+: 445.1330; found:
HRMS (ESI +ve): m/z calcd for C19H25N3O7 [M + H]+: 408.1765; found:
445.1333.
408.1765.
Ethyl 4-(2-(2-((tert-Butoxycarbonyl)amino)ethyl)phenoxy)-2-di-
azo-3-oxobutanoate (9)
Ethyl 4-((1-(((tert-Butoxycarbonyl)amino)methyl)naphthalen-2-
yl)oxy)-2-diazo-3-oxobutanoate (8c)
Following GP4, tert-butyl (2-hydroxyphenethyl)carbamate 6 (150 mg,
0.63 mmol) and other reagents were used in the indicated quantities
with a reaction time of 15.5 h. Yield 130 mg (53%); pale green oil.
1H NMR (400 MHz, CDCl3):  = 7.19–7.16 (m, 2 H, Ar), 6.94 (ddd, J =
7.47, 7.45 1.06 Hz, 1 H, Ar), 6.74 (d, J = 8.44 Hz, 1 H, Ar), 5.20 (s, 2 H,
OCH2C(O)), 4.99 (br s, 1 H, NH), 4.37 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.44
(td, J = 6.05, 5.89 Hz, 2 H, ArCH2CH2), 2.92 (t, J = 6.6 Hz, 2 H,
ArCH2CH2), 1.43 (s, 9 H, C(CH3)3), 1.39 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 187.04, 161.17, 156.16, 156.01,
131.09, 128.26, 127.57, 121.53, 111.30, 78.77, 75.25 (C=N2), 70.80,
61.92, 30.79 (ArCH2CH2), 28.41 (3 C, C(CH3)3), 28.38 (ArCH2CH2),
14.34.
In this case, 1.5 equiv. of ethyl 4-chloro-2-diazo-3-oxobutanoate and
2 equiv. of K2CO3 were used. Following GP4, tert-butyl ((2-hy-
droxynaphthalen-1-yl)methyl)carbamate (5c) (173 mg, 0.63 mmol),
K2CO3 (175 mg, 1.27 mmol), 18-crown-6 (17 mg, 0.064 mmol), KI (11
mg, 0.066 mmol), and ethyl 4-chloro-2-diazo-3-oxobutanoate (181
mg, 0.95 mmol) were used in HPLC-grade CH3CN (3 mL) with a reac-
tion time of 24 h. Yield 196 mg (72%); colorless solid; mp 122.2–123.1
°C (decomp.).
1H NMR (400 MHz, CDCl3):  = 8.27 (d, J = 8.6 Hz, 1 H, Ar), 7.80–7.77
(m, 2 H, Ar), 7.56 (dd, J = 7.56, 7.42 Hz, 1 H, Ar), 7.39 (ddd, J = 8.0, 6.8,
1.1 Hz, 1 H, Ar), 7.16 (d, J = 9.1 Hz, 1 H, Ar), 5.56 (t, J = 5.2 Hz, 1 H, NH),
5.37 (s, 2 H, OCH2C(O)), 4.92 (d, J = 5.6 Hz, 2 H, ArCH2), 4.38 (q, J = 7.1
Hz, 2 H, OCH2CH3), 1.46 (s, 9 H, C(CH3)3), 1.39 (t, J = 7.1 Hz, 3 H,
OCH2CH3).
HRMS (ESI +ve): m/z calculated for C19H25N3O6 [M + Na]+: 414.1636;
found: 414.1638.
13C NMR (101 MHz, CDCl3):  = 187.67, 161.13, 156.00, 153.98,
132.84, 129.68, 129.59, 128.28, 127.14, 124.08, 123.89, 121.27,
113.73, 78.90, 75.30 (C=N2), 72.01, 61.97, 34.92 (ArCH2), 28.48 (3 C,
C(CH3)3), 14.34.
HRMS (ESI +ve): m/z calcd for C22H25N3O6 [M + Na]+: 450.1636; found:
450.1647.
Alkyl 4H-Benzo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-carboxyl-
ates 10a–g; General Procedure 5 (GP5)
TFA (0.386 mL, 5 mmol) was added to a solution of the appropriate
alkyl
4-(2-((tert-butoxycarbonyl)amino)phenoxy)-2-diazo-3-oxo-
butanoate 7a–g (0.5 mmol) in DCM (4 mL), and the reaction mixture
was stirred at room temperature for 18 h. The organic solvent was
washed with a sat. solution of NaHCO3 (2 × 4 mL) and H2O (4 mL). The
organic layer was dried over Na2SO4, filtered, and concentrated under
reduced pressure to afford the corresponding alkyl 4H-ben-
zo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-carboxylate.
Ethyl 4-(2-(((tert-Butoxycarbonyl)amino)methyl)-4-chlorophen-
oxy)-2-diazo-3-oxobutanoate (8d)
Following GP4, tert-butyl (5-chloro-2-hydroxybenzyl)carbamate (5d)
(163 mg, 0.63 mmol) and other reagents were used in the indicated
quantities with a reaction time of 15 h. Yield 169 mg (65%); colorless
solid; mp 79.8–81.1 °C (decomp.).
Ethyl 4H-Benzo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-carboxylate
(10a)
1H NMR (400 MHz, CDCl3):  = 7.30 (br s, 1 H, 3-Ar, overlapping with
CDCl3), 7.17 (dd, J = 8.7, 2.7 Hz, 1 H, 5-Ar), 6.71 (d, J = 8.8 Hz, 1 H, 6-
Ar), 5.56 (br s, 1 H, NH), 5.19 (s, 2 H, OCH2C(O)), 4.40–4.34 (m, 4 H,
OCH2CH3 and ArCH2 overlapping), 1.47 (s, 9 H, C(CH3)3), 1.39 (t, J = 7.1
Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 186.80, 161.08, 156.07, 154.67,
129.85, 129.60, 128.06, 126.45, 112.85, 79.43, 75.36 (C=N2), 71.26,
62.02, 40.43 (ArCH2), 28.42 (3 C, C(CH3)3), 14.33.
Following GP5, ethyl 4-(2-((tert-butoxycarbonyl)amino)phenoxy)-2-
diazo-3-oxobutanoate (7a) (182 mg, 0.5 mmol) and the indicated
amount of TFA were used to obtain the title compound as a brown
solid (102 mg, 83%); mp 130.5–131.8 °C.
1H NMR (400 MHz, CDCl3):  = 8.11 (dd, J = 8.0, 1.6 Hz, 1 H, 9-Ar), 7.35
(ddd, J = 8.0, 7.9, 1.6 Hz, 1 H, 7-Ar), 7.23–7.12 (m, 2 H, 8-Ar and 6-Ar
overlapping), 5.66 (s, 2 H, ArOCH2), 4.49 (q, J = 7.1 Hz, 2 H, OCH2CH3),
1.47 (t, J = 7.2 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 160.63, 145.22, 134.86, 131.49,
HRMS (ESI +ve): m/z calcd for C18H22ClN3O6 [M + Na]+: 434.1089;
129.76, 123.17, 123.16, 117.89, 116.95, 62.22, 61.61, 14.32.
found: 434.1098.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

J
A. V. Budeev et al.
Paper
Synthesis
HRMS (ESI +ve): m/z calcd for C12H11N3NaO3 [M + Na]+: 268.0693;
found: 268.0681.
er was dried over Na2SO4, filtered, and concentrated under reduced
pressure to afford the title compound as a beige solid (62 mg, 47%);
mp 207.8–208.7 °C.
1H NMR (400 MHz, CDCl3):  = 7.43 (d, J = 2.7 Hz, 1 H, 9-Ar), 6.97 (d, J =
8.7 Hz, 1 H, 6-Ar), 6.65 (dd, J = 8.8, 2.7 Hz, 1 H, 7-Ar), 5.54 (s, 2 H,
ArOCH2), 4.48 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.76 (br s, 2 H, NH2), 1.46
(t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 160.71, 142.41, 137.55, 134.75,
132.04, 123.69, 118.60, 116.12, 103.02, 62.04, 61.54, 14.32.
Ethyl 8-Methyl-4H-benzo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-
carboxylate (10b)
Following GP5, ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-methyl-
phenoxy)-2-diazo-3-oxobutanoate (7b) (190 mg, 0.5 mmol) and the
indicated amount of TFA were used to obtain the title compound as a
brownish solid (119 mg, 91%); mp 110.9–111.7 °C.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 2.1 Hz, 1 H, 9-Ar), 7.13 (dd,
J = 8.5, 2.1 Hz, 1 H, 7-Ar), 7.04 (d, J = 8.4 Hz, 1 H, 6-Ar), 5.61 (s, 2 H,
ArOCH2), 4.48 (q, J = 7.1 Hz, 2 H, OCH2CH3), 2.41 (s, 3 H, ArCH3), 1.47
(t, J = 7.1 Hz, 3 H, OCH2CH3).
HRMS (ESI +ve): m/z calcd for C12H12N4O3 [M + Na]+: 283.0802; found:
283.0807.
Ethyl 8-(Pyrrolidine-1-carbonyl)-4H-benzo[b][1,2,3]triazolo[1,5-d]-
[1,4]oxazine-3-carboxylate (10f)
13C NMR (101 MHz, CDCl3):  = 160.67, 143.01, 134.81, 133.20,
131.60, 130.29, 122.86, 117.56, 117.15, 62.14, 61.57, 20.77, 14.32.
HRMS (ESI +ve): m/z calcd for C13H13N3NaO3 [M + Na]+: 282.0849;
found: 282.0846.
Following GP5, ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-(pyrroli-
dine-1-carbonyl)phenoxy)-2-diazo-3-oxobutanoate (7f) (63 mg,
0.137 mmol) and TFA (0.105 mL, 1.37 mmol) were used in DCM (1.1
mL). In this case, the reaction time was 23 h. Yield 28 mg (60%); beige
solid; mp 167.4–168.3 °C.
Ethyl 8-(tert-Butyl)-4H-benzo[b][1,2,3]triazolo[1,5-d][1,4]oxa-
1H NMR (400 MHz, DMSO-d6):  = 8.13 (d, J = 2.0 Hz, 1 H, 9-Ar), 7.59
(dd, J = 8.5, 2.0 Hz, 1 H, 7-Ar), 7.27 (d, J = 8.4 Hz, 1 H, 6-Ar), 5.78 (s, 2
H, ArOCH2), 4.36 (q, J = 7.0 Hz, 2 H, OCH2CH3), 3.49 (t, J = 6.5 Hz, 4 H,
pyrrolidine), 1.88 (p, J = 6.3, 5.9 Hz, 4 H, pyrrolidine), 1.35 (t, J = 7.1
Hz, 3 H, OCH2CH3).
zine-3-carboxylate (10c)
Following GP5, ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-(tert-bu-
tyl)phenoxy)-2-diazo-3-oxobutanoate (7c) (210 mg, 0.5 mmol) and
the indicated amount of TFA were used to obtain the title compound
as a brown solid (132 mg, 87%); mp 97.6–99.1 °C.
13C NMR (101 MHz, DMSO-d6):  = 166.78, 160.26, 146.38, 134.77,
132.62, 132.13, 129.31, 122.53, 117.94, 115.88, 62.99, 61.56, 49.48,
46.66, 26.51, 24.35, 14.54.
1H NMR (400 MHz, CDCl3):  = 8.12 (d, J = 2.4 Hz, 1 H, 9-Ar), 7.36 (dd,
J = 8.7, 2.4 Hz, 1 H, 7-Ar), 7.08 (d, J = 8.6 Hz, 1 H, 6-Ar), 5.61 (s, 2 H,
ArOCH2), 4.49 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.47 (t, J = 7.1 Hz, 3 H,
OCH2CH3), 1.39 (s, 9 H, C(CH3)3).
HRMS (ESI +ve): m/z calcd for C12H12N4O3 [M + Na]+: 365.1220; found:
13C NMR (101 MHz, CDCl3):  = 160.71, 146.87, 142.90, 134.82,
131.65, 126.74, 122.75, 117.34, 113.90, 62.14, 61.58, 34.73, 31.32 (3 C,
C(CH3)3), 14.33.
365.1229.
Methyl 8-Chloro-4-methyl-4H-benzo[b][1,2,3]triazolo-
[1,5-d][1,4]oxazine-3-carboxylate (10g)
HRMS (ESI +ve): m/z calcd for C16H19N3NaO3 [M + Na]+: 324.1319;
found: 324.1315.
Following GP5, methyl 4-(2-((tert-butoxycarbonyl)amino)-4-chloro-
phenoxy)-2-diazo-3-oxopentanoate 7g (125 mg, 0.314 mmol) and
TFA (0.241 mL, 3.14 mmol) were used in DCM (2 mL) to afford the ti-
tle compound as a beige solid (78 mg, 89%); mp 151.2–152.3 °C.
Ethyl 8-Chloro-4H-benzo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-
carboxylate (10d)
1H NMR (400 MHz, CDCl3):  = 8.11 (d, J = 2.5 Hz, 1 H, 9-Ar), 7.31 (dd,
J = 8.8, 2.5 Hz, 1 H, 7-Ar, overlapping with CDCl3), 7.10 (d, J = 8.7 Hz, 1
H, 6-Ar), 6.13 (q, J = 6.8 Hz, 1 H, CHCH3), 4.02 (s, 3 H, OCH3), 1.62 (d, J =
6.8 Hz, 3H, CHCH3).
Following GP5, ethyl 4-(2-((tert-butoxycarbonyl)amino)-4-chloro-
phenoxy)-2-diazo-3-oxobutanoate (7d) (200 mg, 0.5 mmol) and the
indicated amount of TFA were used to obtain the title compound as a
beige solid (118 mg, 84%); mp 139.6–140.8 °C.
13C NMR (101 MHz, CDCl3):  = 160.91, 142.01, 135.25, 134.22,
129.80, 127.98, 122.93, 119.84, 116.96, 69.93, 52.46, 19.72.
HRMS (ESI +ve): m/z calcd for C12H10ClN3O3 [M + Na]+: 302.0303;
found: 302.0310.
1H NMR (400 MHz, CDCl3):  = 8.10 (d, J = 2.4 Hz, 1 H, 9-Ar), 7.30 (dd,
J = 8.8, 2.5 Hz, 1 H, 7-Ar, overlapping with CDCl3), 7.10 (d, J = 8.8 Hz, 1
H, 6-Ar), 5.65 (s, 2 H, ArOCH2), 4.48 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.46
(t, J = 7.2 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 160.44, 143.68, 135.11, 131.37,
129.65, 128.31, 123.55, 119.13, 117.10, 62.41, 61.74, 14.31.
Ethyl 4H,10H-Benzo[f][1,2,3]triazolo[5,1-c][1,4]oxazepine-3-car-
HRMS (ESI +ve): m/z calcd for C16H19N3NaO3 [M + Na]+: 302.0303;
boxylates 11a–e; General Procedure 6 (GP6)
found: 302.0301.
TFA (0.141 mL, 1.84 mmol) was added to a solution of the appropriate
ethyl 4-(2-(((tert-butoxycarbonyl)amino)methyl)phenoxy)-2-diazo-
3-oxobutanoate 8a–e (0.18 mmol) in DCM (1.2 mL), and the reaction
mixture was stirred at room temperature for 18 h. The organic sol-
vent was removed in vacuo. The residue was dissolved in MeOH (2
mL), and AcONa (121 mg, 1.47 mmol) was added. The reaction mix-
ture was stirred at 45 °С for 22.5 h (TLC control). The MeOH was evap-
orated in vacuo. The residue was dissolved in DCM (5 mL) and washed
with a sat. solution of NaHCO3 (2 × 5 mL) and H2O (5 mL). The organic
layer was dried over Na2SO4, filtered, and concentrated under reduced
pressure to afford the corresponding ethyl 4H,10H-benzo[f][1,2,3]tri-
azolo[5,1-c][1,4]oxazepine-3-carboxylate.
Ethyl 8-Amino-4H-benzo[b][1,2,3]triazolo[1,5-d][1,4]oxazine-3-
carboxylate (10e)
TFA (0.576 mL, 7.5 mmol) was added to a solution of ethyl 4-(2,4-
bis((tert-butoxycarbonyl)amino)phenoxy)-2-diazo-3-oxobutanoate
(7e) (240 mg, 0.5 mmol) in DCM (4 mL), and the reaction was stirred
at room temperature overnight. The organic solvent was removed in
vacuo. The residue was dissolved in EtOAc (10 mL) and washed with a
sat. solution of NaHCO3 (2 × 10 mL) and H2O (10 mL). The organic lay-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L

K
A. V. Budeev et al.
Paper
Synthesis
Ethyl 4H,10H-Benzo[f][1,2,3]triazolo[5,1-c][1,4]oxazepine-3-car-
boxylate (11a)
1H NMR (400 MHz, CDCl3):  = 7.42–7.39 (m, 2 H, Ar), 7.21 (d, J = 9.2
Hz, 1 H, Ar), 5.67 (s, 2 H), 5.52 (s, 2 H), 4.41 (q, J = 7.1 Hz, 2 H,
OCH2CH3), 1.41 (t, J = 7.1 Hz, 3 H, OCH2CH3).
13C NMR (101 MHz, CDCl3):  = 161.01, 156.43, 138.50, 136.08,
131.17, 130.76, 129.75, 129.13, 123.30, 68.09, 61.38, 50.73, 14.31.
Following GP6, ethyl 4-(2-(((tert-butoxycarbonyl)amino)methyl)phen-
oxy)-2-diazo-3-oxobutanoate (8a) (70 mg, 0.18 mmol) and other re-
agents in the indicated quantities were used. In this case, the crude
product was purified by column chromatography to obtain the title
compound as a brownish solid (33 mg, 69%); mp 102.1–103.3 °C.
1H NMR (400 MHz, CDCl3):  = 7.44 (ddd, J = 7.76, 7.75, 1.68 Hz, 1 H,
7-Ar), 7.40 (dd, J = 7.5, 1.6 Hz, 1 H, 9-Ar), 7.29–7.26 (m, 1 H, 6-Ar,
overlapping with CDCl3), 7.22 (ddd, J = 7.6, 7.5, 1.2 Hz, 1 H, 8-Ar), 5.72
(s, 2 H), 5.53 (s, 2 H), 4.41 (q, J = 7.1 Hz, 2 H, OCH2CH3), 1.42 (t, J = 7.1
Hz, 3 H, OCH2CH3).
HRMS (ESI +ve): m/z calcd for C13H12ClN3O3 [M + Na]+: 316.0459;
found 316.0461.
Ethyl 8-Nitro-4H,10H-benzo[f][1,2,3]triazolo[5,1-c][1,4]oxaze-
pine-3-carboxylate (11e)
Following GP6, ethyl 4-(2-(((tert-butoxycarbonyl)amino)methyl)-4-
nitrophenoxy)-2-diazo-3-oxobutanoate (8e) (78 mg, 0.18 mmol) and
other reagents in the indicated quantities were used to afford the title
compound as a beige solid (39 mg, 69%); mp 163.9–164.9 °C (de-
comp.).
13C NMR (101 MHz, CDCl3):  = 161.10, 157.97, 138.84, 135.96,
131.32, 129.12, 128.34, 125.65, 121.85, 68.07, 61.28, 51.25, 14.33.
HRMS (ESI +ve): m/z calcd for C13H13N3O3 [M + Na]+: 282.0849; found:
1H NMR (400 MHz, CDCl3):  = 8.35–8.30 (m, 2 H, 7-Ar and 9-Ar over-
lapping), 7.43–7.37 (m, 1 H, 6-Ar), 5.83 (s, 2 H), 5.66 (s, 2 H), 4.44 (q,
J = 7.1 Hz, 2 H, OCH2CH3), 1.44 (t, J = 7.1 Hz, 3 H, OCH2CH3).
282.0849.
Ethyl 6-Methoxy-4H,10H-benzo[f][1,2,3]triazolo[5,1-c][1,4]oxaze-
pine-3-carboxylate (11b)
13C NMR (101 MHz, CDCl3):  = 162.49, 160.87, 144.45, 137.52,
Following GP6, ethyl 4-(2-(((tert-butoxycarbonyl)amino)methyl)-6-
methoxyphenoxy)-2-diazo-3-oxobutanoate (8b) (75 mg, 0.18 mmol)
and other reagents in the indicated quantities were used to afford the
title compound as a colorless solid (39 mg, 73%); mp 121.1–122.3 °C
(decomp.).
136.47, 127.82, 126.77, 125.11, 123.11, 66.81, 61.57, 50.63, 14.29.
HRMS (ESI +ve): m/z calcd for C13H12N4O5 [M + Na]+: 327.0700; found:
327.0700.
1H NMR (400 MHz, CDCl3):  = 7.16 (dd, J = 8.4, 7.6 Hz, 1 H, Ar), 7.03
(dd, J = 8.5, 1.5 Hz, 1 H, Ar), 6.97 (dd, J = 7.6, 1.4 Hz, 1 H, Ar), 5.71 (s, 2
H), 5.53 (s, 2 H), 4.41 (q, J = 7.1 Hz, 2 H, OCH2CH3), 3.94 (s, 3 H, OCH3),
1.41 (t, J = 7.2 Hz, 3 H, OCH2CH3).
Funding Information
This research was supported by the Russian Science Foundation (proj-
ect grant 20-13-00024).
R
usianScience
F
o
u
n
datio
n
(20-13-0
0
0
2
4)
13C NMR (101 MHz, CDCl3):  = 161.05, 152.24, 146.10, 139.04,
136.00, 130.26, 126.07, 120.34, 113.69, 67.58, 61.24, 56.05, 51.13,
14.34.
Acknowledgment
HRMS (ESI +ve): m/z calcd for C14H15N3O4 [M + Na]+: 312.0955; found:
312.0960.
We thank the Magnetic Resonance Research Centre and the Chemical
Analysis and Materials Research Centre of Saint Petersburg State Uni-
versity Research Park for obtaining the analytical data.
Ethyl 8H,13H-Naphtho[1,2-f][1,2,3]triazolo[5,1-c][1,4]oxazepine-
9-carboxylate (11c)
Supporting Information
Following GP6, ethyl 4-((1-(((tert-butoxycarbonyl)amino)meth-
yl)naphthalen-2-yl)oxy)-2-diazo-3-oxobutanoate (8c) (79 mg, 0.18
mmol) and other reagents in the indicated quantities were used to af-
ford the title compound as a beige solid (45 mg, 79%); mp 146.7–
147.5 °C.
Supporting information for this article is available online at
https://doi.org/10.1055/a-1348-9031. Copies of the 1H and 13C NMR
spectra are included. Su
p
p
orti
n
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n
Su
p
p
ortingInformatio
n
1H NMR (400 MHz, CDCl3):  = 8.17 (d, J = 8.5 Hz, 1 H, Ar), 7.94 (d, J =
8.7 Hz, 1 H, Ar), 7.90 (d, J = 8.2 Hz, 1 H, Ar), 7.64 (ddd, J = 8.4, 6.9, 1.4
Hz, 1 H, Ar), 7.52 (ddd, J = 8.1, 6.9, 1.1 Hz, 1 H, Ar), 7.42 (d, J = 8.8 Hz, 1
H, Ar), 6.19 (s, 2 H), 5.60 (s, 2 H), 4.41 (q, J = 7.1 Hz, 2 H, OCH2CH3),
1.41 (t, J = 7.1 Hz, 3 H, OCH2CH3).
References
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13C NMR (101 MHz, CDCl3):  = 161.09, 156.16, 138.91, 136.00,
131.75, 131.44, 130.72, 128.93, 127.75, 125.72, 123.12, 122.38,
120.77, 67.92, 61.28, 45.56, 14.33.
HRMS (ESI +ve): m/z calcd for C17H15N3O3 [M + Na]+: 332.1006; found:
332.1008.
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Ethyl 8-Chloro-4H,10H-benzo[f][1,2,3]triazolo[5,1-c][1,4]oxaze-
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Following GP6, ethyl 4-(2-(((tert-butoxycarbonyl)amino)methyl)-4-
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–L