One-pot reductive mono-n-alkylation of aromatic nitro compounds using nitriles as alkylating reagents

Article abstract of DOI:10.1080/00397911.2010.493627

A one-pot, simple, selective, and efficient protocol for the synthesis of aromatic secondary amines from various nitro arenes and nitriles in the presence of 10% Pd/C catalyst under H₂ at atmospheric pressure and ambient temperature in tetrahydrofuran is illustrated. The scope and limitations of this method have been examined.

Full text of DOI:10.1080/00397911.2010.493627

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One-Pot Reductive Mono-N-alkylation of
Aromatic Nitro Compounds Using Nitriles
as Alkylating Reagents
Subhasish Neogi a & Dinabandhu Naskar a
a Syngene International Ltd. , Bangalore, India
Published online: 02 May 2011.
To cite this article: Subhasish Neogi & Dinabandhu Naskar (2011) One-Pot Reductive Mono-
N-alkylation of Aromatic Nitro Compounds Using Nitriles as Alkylating Reagents, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:13, 1901-1915, DOI: 10.1080/00397911.2010.493627
To link to this article: http://dx.doi.org/10.1080/00397911.2010.493627
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Synthetic Communications1, 41: 1901–1915, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.493627
ONE-POT REDUCTIVE MONO-N-ALKYLATION OF
AROMATIC NITRO COMPOUNDS USING NITRILES AS
ALKYLATING REAGENTS
Subhasish Neogi and Dinabandhu Naskar
Syngene International Ltd., Bangalore, India
GRAPHICAL ABSTRACT
Abstract A one-pot, simple, selective, and efficient protocol for the synthesis of aromatic
secondary amines from various nitro arenes and nitriles in the presence of 10% Pd/C cata-
lyst under H2 at atmospheric pressure and ambient temperature in tetrahydrofuran is illu-
strated. The scope and limitations of this method have been examined.
Keywords Amination nitro compound; one pot; reductive amination
INTRODUCTION
Amines and their derivatives are highly versatile building blocks for various
organic substrates and are essential precursors to a variety of biologically active
compounds. Because of their interesting biological and physiological activities, the
secondary amine moiety has played a central role in the chemotherapeutics of
numerous diseases[1] and also has been an extremely important pharmacophore in
numerous biologically active compounds in the area of drug discovery.[2] The syn-
thesis of secondary amines has also spurred intense activity in solid-phase synthesis[3]
as well as combinatorial library generation,[4] where these amines can be utilized as
an important scaffold for further manipulation.
It is also well known that aromatic secondary amines play an important role in
a number of areas,[5] which include industrial, pharmaceutical, and agrochemical
applications. On an industrial level, these compounds have served as antioxidants
in petrochemicals for polymer and rubber manufacturing processes.[6] Also, they
have served well in applications such as photography, xeroxography, pigments, dyes,
and electronic materials.[7] Additionally, aryl amines can be useful in small quantities
Received November 4, 2009.
Address correspondence to Dinabandhu Naskar, Syngene International Ltd., Biocon Park, Plot
Nos. 2 and 3, Bommasandra IV Phase, Jigani Link Road, Bangalore 560 099, India. E-mail:
dinabandhu.naskar@syngeneintl.com
1901

1902
S. NEOGI AND D. NASKAR
as additives to gasoline (they substantially improve the octane rating).[8a] More
importantly, N-alkylated aromatic amines are also well utilized in the synthesis of
numerous pharmaceutical compounds. One of the most revealing facts is that a
significant number of the 20 top-selling pharmaceuticals in 1994 contained aromatic
carbon–nitrogen bonds.[8b] With the growing repertoire of applications, developing
efficient methods for the synthesis of these amines as useful intermediates draws
much attention.
Reported methods for the synthesis of secondary amines include base-mediated
N-alkylation using toxic and corrosive alkylating agents,[9] reductive amination,[10]
metal-catalyzed reactions,[11] alkylative amination,[12] and other alkylation meth-
ods,[13] but most of these suffer from many disadvantages. It is reported that
reductive amination of carbonyl compounds provides secondary aromatic amines.[14]
There are also literature reports on reductive alkylation of amines using nitrile as the
alkylating agent with hydrogen in the presence of different types of catalyst, but only
a few examples of selective mono-N-alkylation have been reported.[15] Some of these
procedures are limited to very few substrates and require large quantities of amine
and elevated hydrogen pressure or higher temperatures. Herein, we report a one-pot,
selective, and efficient synthesis of aromatic secondary amines at ambient tempera-
ture using various aromatic nitro compounds and nitriles as alkylating reagents in
the presence of 10% Pd=C under H2 at atmospheric pressure in tetrohydrofuran
(THF) as solvent.
RESULTS AND DISCUSSION
To find a suitable solvent for better yield for the synthesis of secondary aro-
matic amines, the reaction was performed in different solvents and monitored by
liquid chromatography–mass spectrometry (LCMS; Table 1). Entry 5 was found
to have the best condition for the reaction. Thus, 3,4-dimethylnitrobenzene was
Table 1. Optimization of solvents
Entry
Solvent
Time (h)
Yield (LCMS)a
1
2
3
4
5
Toluene
MeOH
EtOAc
EtOH
THF
25
25
25
25
25
21
75
88
91
99
aLCMS yield of crude material.
Scheme 1.

REDUCTIVE MONO-N-ALKYLATION
1903
Table 2. One-pot reductive amination of 3,4-dimethylnitrobenzene with various nitriles
Entry
1
Nitrile
Mono-alkylated product
Time (h)
25
Yield (%)a
CH3-CN
95
2
30
63
3
4
5
40
40
48
42
37
35
R2-CN
Note. R1 ¼ 3,4-Dimethyl-C6H4-; R2 ¼ p-OMe-Bn- (entry 4).
aAll yields refer to pure, isolated products.
treated with acetonitrile in one pot at ambient temperature in the presence of 10%
Pd=C under H2 at atmospheric pressure in THF as solvent and monitored by LCMS
(Scheme 1). The solvent was removed, and the residue was purified by column
chromatography to afford 95% of the desired product.
Table 3. One-pot reductive amination of o-, m-, and p-methylnitrobenzene with various nitriles
Entry
1
Nitrile
Mono-alkylated product
Time (h)
24
Yield (%)a
CH3-CN
88
2
3
24
48
70
68
4
5
48
48
54
53
6
7
40
40
43
32
R2-CN
Note. R1 ¼ p-Me-C6H4- (entries 1–5); o-Me-C6H4- (entry 6); m-Me-C6H4- (entry 7); R2 ¼ p-OMe-Bn-
(entry 7).
aAll yields refer to pure, isolated products.

1904
S. NEOGI AND D. NASKAR
Table 4. One-pot reductive amination of p-methoxynitrobenzene with various nitriles
Entry
1
Nitrile
Mono-alkylated product
Time (h)
26
Yield (%)a
CH3-CN
84
2
3
48
46
57
55
4
38
30
Note.
.
aAll yields refer to pure, isolated products.
Encouraged by these results, the scope of the reaction of various nitro com-
pounds and various nitriles was explored further for a selective and efficient synthesis
of aromatic secondary amines or CꢀN bond formation in the presence of 10% Pd=C
under H2 at atmospheric pressure in THF. Commercially available nitro compounds
and nitriles were subjected to our standard condition to achieve various secondary
aromatic amines.
The Pd=C-catalyzed reduction of 3,4-dimethylnitrobenzene to provide
mono-N-alkylation using various nitriles is summarized in Table 2. Equimolar
amounts of nitro and nitriles were treated with 0.5 equivalent of 10% Pd=C in
THF as solvent under hydrogen at atmospheric pressure at ambient temperature
in one pot. An excellent yield of monoalkylated product was obtained using acetoni-
trile and isobutyronitrile (entry 1 and 2). The moderate to poor yields was observed
in case of 3-hydroxy propionitrile, 4-methoxy benzyl nitrile, and butyronitrile
(entries 3, 4, and 5).
Table 5. One-pot reductive amination of nitrobenzene with various nitriles
Entry
Nitrile
Mono-alkylated product
Time (h)
Yield (%)a
1
2
3
CH3-CN
28
42
44
68
40
35
Note. R1 ¼ Ph.
aAll yields refer to pure, isolated products.

REDUCTIVE MONO-N-ALKYLATION
1905
Table 6. One-pot reductive amination of o-, m-, p-hydroxynitrobenzenes and o-methyl-m-hydroxy nitro-
benzene with various nitriles
Entry
1
Nitrile
Mono-alkylated product
Time (h)
22
Yield (%)a
87
CH3-CN
2
43
62
3
4
40
48
60
33
R3-CN
R2-CN
5
40
31
6
7
R2-CN
44
30
33
48
CH3-CN
8
38
32
9
48
30
31
30
10
Notes. R1 ¼ o-OH-C6H4- (entries 1–4, 8, 9); p-OH-C6H4- (entries 5, 10); m-OH-C6H4- (entry 6);
R3 ¼ Bn- (entry 4); R1 ¼ m-OH-o-Me-C6H4- (entry 7); R2 ¼ p-MeO-Bn- (entries 5, 6).
aAll yields refer to pure, isolated products.
We next examined the mono-N-alkylation of other nitro compounds (Tables 3,
4, and 5) using various nitriles. Excellent yields from mono-N-alkylation using acet-
onitrile, isobutyronitrile, ethylcyanoacetate, and 3-hydroxy propionitrile were
observed. Using benzyl nitrile, the reaction affords more moderate yields under
the same conditions. Poor to moderate yields were observed in cases of butyronitrile
and propionitrile. We have observed that with increasing side chain size of the
aliphatic nitrile, the yield of the corresponding product decreases.
It is interesting to note that the mono-N-alkylation of hydroxynitro com-
pounds and N-Boc indoline were good under the present conditions (Tables 6 and
7). Excellent yields were observed in cases of acetonitrile, ethylcyanoacetate, and
3-hydroxypropionitrile. The reaction with benzyl nitriles affords good to moderate
yields, but when using the long-chain aliphatic nitriles the reaction affords moderate
to poor yields.
On the basis of these results, amidine formation by the nucleophilic attack
of in situ–generated amines on the nitrile carbon suitably activated by the mild

1906
S. NEOGI AND D. NASKAR
Table 7. One-pot reductive amination of N-Boc-indoline with various nitriles
Entry
1
Nitrile
Mono-alkylated product
Time (h)
Yield (%)a
94
CH3-CN
24
2
3
28
30
52
49
4
5
28
48
40
33
R2-CN
Note. R2 ¼ Bn.
.
aAll yields refer to pure, isolated products.
Scheme 2. Presumed mechanism.
coordination of Pd is a key step for the selective alkylation (Scheme 2); however, the
exact intermediate is not yet known.
CONCLUSION
In summary, we have developed a one-pot, simple, selective, and efficient pro-
tocol for the synthesis of aromatic secondary amines using various nitro compounds
and various nitriles as alkylating reagents in the presence of 10% Pd=C catalyst
under H2 at atmospheric pressure and ambient temperature in THF as solvent.
The reaction is carried out at ambient temperature and proceeds smoothly and selec-
tively with excellent to moderate yields. Our protocol is facile and economical for the
synthesis of various aromatic secondary amines.

REDUCTIVE MONO-N-ALKYLATION
1907
EXPERIMENTAL
General Procedure for One-Pot Reductive Mono-N-alkylation of
Aromatic Nitro Compounds Using Nitriles as Alkylating Agent
To a stirring mixture of 3,4-dimethylnitrobenzene (151 mg, 1 mmol) and acet-
onitrile (41 mg, 1 mmol) in THF (3 mL), 10% Pd=C (60 mg, 0.56 mmol) was added.
The reaction mixture was stirred under hydrogen atmospheric pressure (balloon)
at ambient temperature for 25 h. The reaction mixture was filtered through celite,
and the solid was washed with THF (15 mL). The solvent was removed under
reduced pressure. The crude material was purified through a bed of silicagel
(60–120 mesh) using a solution of ethyl acetate and hexane (1:10) to afford the pure
product as yellow oil (142 mg, 95%). Rf ¼ 0.72 (30% EtOAc–hexane); 1H NMR
(CDCl3, 400 MHz): d 1.24–1.27 (t, 3H), 2.17 (s, 3H), 2.22 (s, 3H), 3.12–3.18 (q,
2H), 6.40–6.43 (d, J ¼ 8.04, 1H), 6.47 (s, 1H), 6.95–6.97 (d, J ¼ 8, 1H). 13C NMR
(CDCl3, 100 MHz): d 14.91, 18.61, 19.97, 38.81, 110.28, 114.69, 125.24, 130.18,
137.17, 146.53. LCMS (UV): 150.2 (M þ Hþ).
Selected Data
3,4-Dimethyl-N-ethylbenzenamine (Table 2, Entry 1). Yellow liquid,
Rf ¼ 0.72 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 5.07 min, 98.52% purity. H NMR (CDCl3, 400 MHz): d 1.24–1.27 (t, 3H),
2.17 (s, 3H), 2.22 (s, 3H), 3.12–3.18 (q, 2H), 6.40–6.43 (d, J ¼ 8.04, 1H), 6.47 (s,
1H), 6.95–6.97 (d, J ¼ 8, 1H). 13C NMR (CDCl3, 100 MHz): d 14.91, 18.61, 19.97,
38.81, 110.28, 114.69, 125.24, 130.18, 137.17, 146.53. LCMS (UV): 150.2 (M þ Hþ).
N-Isobutyl-3,4-dimethylaniline (Table 2, Entry 2). Yellow liquid, Rf ¼ 0.68
(30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm par-
ticle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with
a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 5.91 min, 99.72%
purity. 1H NMR (CDCl3, 400 MHz): d 0.99 (s, 3H), 1.00 (s, 3H), 1.87–1.93 (m, 1H),
2.17 (s, 3H), 2.20 (s, 3H), 2.92–2.94 (d, J ¼ 6.8, 2H), 3.60 (broad, 1H), 6.40–6.43 (d,
J ¼ 8.04, 1H), 6.47 (s, 1H), 6.94–6.97 (d, J ¼ 8.04, 1H). 13C NMR (CDCl3, 100 MHz):
d 18.68, 20.06, 20.51, 27.99, 52.26, 110.22, 114.66, 125.06, 130.26, 137.26, 146.67.
LCMS (UV): 178.2 (M þ Hþ).
3-(3,4-Dimethyl-phenylamino)-propan-1-ol (Table 2, Entry 3). Yellow
liquid, Rf ¼ 0.31 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear
gradient over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and
1
UV at Rt ¼ 4.24 min, 98.04% purity. H NMR (DMSO-d6, 400 MHz): d 1.64–1.70
(m, 2H), 2.05 (s, 3H), 2.09 (s, 1H), 2.98–3.02 (m, 2H), 3.47–3.51 (m, 2H),
6.27–6.29 (d, J ¼ 8.04, 1H), 6.36 (s, 1H), 6.80–6.82 (d, J ¼ 8.08, 1H). 13C NMR
(DMSO-d6, 100 MHz): d 18.83, 20.24, 32.55, 57.00, 59.28, 109.95, 114.18, 123.03,
130.29, 136.55, 147.69. LCMS (UV): 180.2 (M þ Hþ).

1908
S. NEOGI AND D. NASKAR
N-(4-Methoxyphenyl)-3,4-dimethyl aniline (Table 2, Entry 4). Yellow
liquid, Rf ¼ 0.67 (30% EtOAc–hexane) analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM. NH4OAc=CH3OH linear
gradient over 12 min, with a flow of 0.8 ml=min, one peak detected by ELS and
1
UV at Rt ¼ 6.02 min, 99.82% purity. H NMR (CDCl3, 400 MHz): d 2.17 (s, 3H),
2.20 (s, 3H), 2.86–2.89 (t, 2H), 3.33–3.37 (t, 2H), 3.81 (s, 3H), 6.46–6.49 (m, 1H),
6.52 (s, 1H), 6.85–6.87 (d, J ¼ 8.6, 2H), 6.95–6.97 (d, J ¼ 8, 1H), 7.13–7.15 (d,
J ¼ 8.56, 2H). 13C NMR (CDCl3, 100 MHz): d 18.71, 20.06, 34.62, 45.68, 55.28,
110.59, 113.97, 115.02, 125.58, 129.72, 130.29, 131.41, 137.33, 146.13, 158.16. LCMS
(UV): 256.2 (M þ Hþ).
3,4-Dimethyl-N-pentylaniline (Table 2, Entry 5). Yellow liquid, Rf ¼ 0.73
(30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm par-
ticle size), mobile phase 0.1% TFA=CH3OH linear gradient over 12 min, with a flow
of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 4.55 min, 99.92% purity.
1H NMR (CDCl3, 400 MHz): d 0.97 (m, 3H), 1.36–1.41 (m, 4H), 1.60–1.64 (m, 2H),
2.17 (s, 3H), 2.21 (s, 3H), 3.07–3.11 (m, 2H), 6.39–6.42 (d, J ¼ 8.04, 1H), 6.45 (s, 1H),
6.94–6.96 (d, J ¼ 8.04, 1H). 13C NMR (CDCl3, 100 MHz): d 14.07, 18.69, 20.05,
22.53, 29.36, 44.40, 110.26, 114.69, 125.17, 130.24, 137.25, 146.67. LCMS (UV):
192.2 (M þ Hþ).
N-Ethyl-4-methylaniline (Table 3, Entry 1). Yellow liquid, Rf ¼ 0.68 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 0.1% TFA=CH3OH linear gradient over 12 min, with a flow of
0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 3.44 min, 99.86% purity.
1H NMR (CDCl3, 400 MHz): d 1.24–1.27 (t, 3H), 2.25 (s, 3H), 3.12–3.17 (m, 2H),
3.51 (broad, 1H), 6.55–6.57 (d, J ¼ 8.4, 2H), 6.99–7.01 (d, J ¼ 8.44, 2H). 13C NMR
(CDCl3, 100 MHz): d 14.85, 20.32, 38.85, 112.99, 126.49, 129.64, 146.03. LCMS
(UV): 136.2 (M þ Hþ).
N-Isobutyl-4-methylaniline (Table 3, Entry 2). Yellow liquid, Rf ¼ 0.63
(30% EtOAc–hexane); analytical HPLC: Symmetry C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 6.07 min, 97.81%
1
purity. H NMR (CDCl3, 400 MHz): d 0.97 (s, 3H), 0.99 (s, 3H), 1.86–1.93 (m,
1H), 2.25 (s, 3H), 2.91–2.93 (d, J ¼ 6.52, 2H), 3.58 (broad, 1H), 6.54–6.56 (d,
J ¼ 8.36, 2H), 6.98–7.01 (d, J ¼ 8.28, 2H). 13C NMR (CDCl3, 100 MHz): d 20.36,
20.50, 27.99, 52.20, 110.04, 112.83, 120.54, 126.14, 129.70, 146.33. LCMS (UV):
164.2 (M þ Hþ).
Ethyl-3-(4-methylphenylamino) propanoate (Table 3, Entry 3). Yellow
liquid, Rf ¼ 0.6 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 0.1% TFA=CH3OH linear gradient
over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 3.13 min, 96.80% purity. H NMR (CDCl3, 400 MHz): d 1.25–1.29 (t, 3H),
2.25 (s, 3H), 2.60–2.63 (t, 2H), 3.42–3.45 (t, 2H), 4.14–4.19 (q, 2H), 6.56–6.59 (d,
J ¼ 8.4, 2H), 6.99–7.02 (d, J ¼ 8.4, 2H). 13C NMR (CDCl3, 100 MHz): d 14.21,
20.38, 33.90, 39.94, 60.61, 113.42, 127.14, 129.75, 129.80, 145.17, 172.46. LCMS
(UV): 208.2 (M þ Hþ).

REDUCTIVE MONO-N-ALKYLATION
1909
3-(p-Tolylamino) propan-1-ol (Table 3, Entry 4). Yellow liquid, Rf ¼ 0.3
(30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm par-
ticle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with
a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 2.42 min, 98.78%
purity. 1H NMR (CDCl3, 400 MHz): d 1.85–1.92 (m, 2H), 2.25 (s, 3H), 3.26–3.29 (m,
2H), 3.81–3.83 (m, 2H), 6.59–6.61 (d, J ¼ 8.4, 2H), 7.00–7.02 (d, J ¼ 8.4, 2H). 13C
NMR (CDCl3, 100 MHz): d 20.40, 31.91, 42.59, 61.89, 113.48, 127.11, 129.75,
145.97. LCMS (UV): 166.2 (M þ Hþ).
N-(2-Phenylethyl)-(4-methyl) aniline (Table 3, Entry 5). Yellow liquid,
Rf ¼ 0.7 (30% EtOAc–hexane); analytical HPLC: Symmetry C18 (4.6 ꢁ 75 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3CN linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
Rt ¼ 5.16 min, 98.21% purity. 1H NMR (CDCl3, 400 MHz): d 2.26 (s, 3H),
2.91–2.95 (t, 2H), 3.39–3.42 (t, 2H), 6.57–6.59 (d, J ¼ 8.4, 2H), 7.00–7.03 (d,
J ¼ 8.4, 2H), 7.23–7.27 (m, 3H), 7.32–7.36 (m, 2H). 13C NMR (CDCl3, 100 MHz):
d 20.33, 35.45, 45.43, 113.23, 126.32, 126.75, 128.52, 128.73, 129.71, 139.32,
145.57. LCMS (UV): 212.2 (M þ Hþ).
c-Oxy-propyl-o-toluidine (Table 3, Entry 6). Yellow liquid, Rf ¼ 0.31 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 3.88 min, 97.66%
1
purity. H NMR (CDCl3, 400 MHz): d 1.92–1.98 (m, 2H), 2.16 (s, 3H), 3.32–3.36
(m, 2H), 3.84–3.89 (m, 2H), 6.67–6.72 (m, 2H), 7.06–7.08 (m, 2H). 13C NMR
(CDCl3, 100 MHz): d 21.51, 31.78, 42.11, 61.91, 110.03, 117.28, 122.36, 127.13,
130.08, 146.20. LCMS (UV): 166.2 (M þ Hþ).
f2-(4-Methoxy-phenyl)-ethylg-m-tolyl-amine (Table 3, Entry 1). Yellow
liquid, Rf ¼ 0.7 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear
gradient over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and
1
UV at Rt ¼ 5.78 min, 98.97% purity. H NMR (CDCl3, 400 MHz): d 2.29 (s, 1H),
2.87–2.91 (t, 2H), 3.35–3.39 (t, 2H), 3.79–3.81 (s, 3H), 6.51–6.52 (m, 2H),
6.58–6.60 (m, 1H), 6.86–6.88 (d, J ¼ 8.28, 2H), 7.09 (m, 1H), 7.12–7.16 (d,
J ¼ 8.36, 2H). 13C NMR (CDCl3, 100 MHz): d 21.55, 34.43, 45.44, 55.21, 110.39,
113.94, 114.01, 118.68, 129.08, 129.64, 131.15, 139.01, 147.65, 158.14. LCMS
(UV): 242.2 (M þ Hþ). Anal. calcd. for C16H19NO: C, 79.63; H, 7.94; N, 5.80.
Found: C, 79.43; H, 8.22; N, 587.
N-Ethyl-4-methoxybenzeneamine (Table 4, Entry 1). Yellow liquid,
Rf ¼ 0.64 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 2.35 min, 99.03% purity. H NMR (CDCl3, 400 MHz): d 1.24–1.27 (t, 3H),
3.12–3.13 (q, 2H), 3.76 (s, 3H), 6.59–6.61 (d, J ¼ 8.92, 2H), 6.79–6.81 (d, J ¼ 8.92,
2H). 13C NMR (CDCl3, 100 MHz): d 15.01, 39.44, 55.82, 114.09, 114.87, 142.78,
152.03. LCMS (UV): 152.2 (M þ Hþ).

1910
S. NEOGI AND D. NASKAR
3-(4-Methoxyphenylamino)-propionic acid ethyl ester (Table 4, Entry 2).
Yellow liquid, Rf ¼ 0.53 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase, 0.1% TFA=CH3OH linear gradient
over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 2.79 min, 95.98% purity. H NMR (CDCl3, 400 MHz): d 1.25–1.29 (t, 3H),
2.59–2.62 (t, 2H), 3.39–3.42 (t, 2H), 3.75 (s, 3H), 4.13–4.19 (q, 2H), 6.61–6.63 (d,
J ¼ 8.92, 2H), 6.79–6.80 (d, J ¼ 8.92, 2H). 13C NMR (CDCl3, 100 MHz): d 14.21,
33.95, 40.59, 55.78, 60.61, 114.65, 114.92, 141.72, 152.43, 172.50. LCMS (UV):
224.2 (M þ Hþ).
(4-Methoxy-phenyl)-pentyl-amine (Table 4, Entry 3). Yellow liquid,
Rf ¼ 0.71 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase, 0.1% TFA=CH3OH linear gradient over 12 min,
with a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 3.89 min,
1
97.37% purity. H NMR (DMSO-d6, 400 MHz): d 0.87–0.89 (m, 3H), 1.30–1.34
(m, 4H), 1.49–1.53 (m, 2H), 2.88–2.93 (m, 2H), 3.61 (s, 1H), 6.47–6.50 (d,
J ¼ 8.92, 2H), 6.67–6.70 (d, J ¼ 8.88, 2H). 13C NMR (CDCl3, 100 MHz): d 14.02,
22.10, 28.60, 29.02, 43.73, 55.34, 112.93, 114.62, 143.49, 150.49. LCMS (UV):
194.2 (M þ Hþ).
N-(2-Phenylethyl)-(4-methoxy)-aniline (Table 4, Entry 4). Yellow liquid,
Rf ¼ 0.68 (30% EtOAc–hexane); analytical HPLC: Symmetry C18 (4.6 ꢁ 75 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3CN linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
Rt ¼ 5.28 min, 98.24% purity. 1H NMR (CDCl3, 400 MHz): 2.91–2.94 (t, 2H),
3.36–3.39 (t, 2H), 3.77 (s, 1H), 6.59–6.62 (d, J ¼ 8.92, 2H), 6.80–6.82 (d, J ¼ 8.92,
2H), 7.23–7.27 (m, 3H), 7.32–7.36 (m, 2H). 13C NMR (CDCl3, 100 MHz): d 35.59,
46.04, 55.81, 114.38, 114.91, 126.39, 128.07, 128.45, 128.60, 128.78, 128.81, 129.15,
139.40, 142.23, 152.18. LCMS (UV): 228.2 (M þ Hþ).
N-Ethyl-N-phenyl-amine (Table 5, Entry 1). Yellow liquid, Rf ¼ 0.67 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 4.11 min, 99.41%
1
purity. H NMR (CDCl3, 400 MHz): d 1.25–1.29 (t, 3H), 3.15–3.20 (q, 2H), 3.83
(broad, 1H), 6.63–6.65 (d, J ¼ 8.4, 2H), 6.71–6.74 (m, 1H), 7.18–7.22 (m, 2H). 13C
NMR (CDCl3, 100 MHz): d 14.82, 38.68, 112.95, 117.46, 129.24, 148.16. LCMS
(UV): 122.2 (M ꢀ Hþ).
N-Propyl-N-phenyl-amine (Table 5, Entry 2). Yellow liquid, Rf ¼ 0.70
(30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm par-
ticle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with
a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 4.79 min, 98.85%
purity. 1H NMR (CDCl3, 400 MHz): d 0.99–1.03 (m, 3H), 1.63–1.69 (m, 2H),
3.08–3.12 (m, 2H), 3.73 (broad, 1H), 6.62–6.64 (d, J ¼ 8.56, 2H), 6.69–6.73 (m,
1H), 7.17–7.27 (m, 2H). 13C NMR (CDCl3, 100 MHz): d 11.58, 22.63, 45.79,
112.69, 117.09, 129.15, 148.34. LCMS (UV): 134.2 (M ꢀ Hþ).

REDUCTIVE MONO-N-ALKYLATION
1911
N-Butyl-N-phenyl-amine (Table 5, Entry 3). Yellow liquid, Rf ¼ 0.71 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 5.36 min, 96.62%
purity. 1H NMR (CDCl3, 400 MHz): d 0.95–0.99 (m, 3H), 1.39–1.49 (m, 2H),
1.59–1.66 (m, 2H), 3.11–3.14 (m, 2H), 3.83 (broad, 1H), 6.63–6.65 (d, J ¼ 8.56,
2H), 6.69–6.73 (m, 1H), 7.17–7.21 (m, 2H). 13C NMR (CDCl3, 100 MHz): d 13.93,
20.31, 31.66, 43.70, 112.71, 117.11, 129.22, 148.49. LCMS (UV): 150.2 (M þ Hþ).
Hydroxy-2-N-ethylaniline (Table 6, Entry 1). White solid, melting
point ¼ 106–107 ꢂC (uncorrected), Rf ¼ 0.58 (30% EtOAc–hexane); analytical HPLC:
Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM NH4OAc=
CH3OH linear gradient over 12 min, with a flow of 0.8 mL=min, one peak detected
1
by ELS and UV at Rt ¼ 2.02 min, 99.69% purity. H NMR (CDCl3, 400 MHz): d
1.28–1.31 (t, 3H), 3.15–3.20 (q, 2H), 4.43 (broad, 1H), 6.63–6.66 (m, 1H),
6.71–6.73 (m, 2H), 6.86–6.90 (m, 1H). 13C NMR (CDCl3, 100 MHz): d 14.94,
38.95, 112.68, 114.25, 117.75, 121.67, 137.15, 143.71. LCMS (UV): 138.2 (M þ Hþ).
3-(2-Hydroxy-phenylamino)-propionic acid ethyl ester (Table 6, Entry 2).
Brown liquid, Rf ¼ 0.42 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS
C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH lin-
ear gradient over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS
and UV at Rt ¼ 4.06 min, 99.03% purity. 1H NMR (CDCl3, 400 MHz): d
1.26–1.30 (t, 3H), 2.63–2.66 (t, 2H), 3.43–3.46 (t, 2H), 4.16–4.22 (q, 2H),
6.69–6.79 (m, 3H), 6.84–6.86 (m, 1H). 13C NMR (CDCl3, 100 MHz): d 14.16,
34.21, 40.44, 60.79, 113.87, 114.64, 119.04, 121.28, 136.08, 144.98. LCMS (UV):
208.2 (M þ Hþ). Anal. calcd. for C11H15NO3: C, 63.14; H, 7.23; N, 6.69. Found:
C, 63.23; H, 7.11; N, 6.64.
2-(3-Hydroxy-propylamino)-phenol (Table 6, Entry 3). Yellow liquid,
Rf ¼ 0.25 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 2.43 min, 98.05% purity. H NMR (CDCl3, 400 MHz): d 1.87–1.91 (m, 2H),
3.27–3.29 (m, 2H), 3.82–3.84 (m, 2H), 6.64–6.66 (m, 1H), 6.72–6.74 (m, 2H),
6.84–6.87 (m, 1H). 13C NMR (CDCl3, 100 MHz): d 31.63, 42.40, 61.74, 112.85,
114.56, 118.28, 121.41, 136.99, 144.15. LCMS (UV): 168.2 (M þ Hþ). Anal. calcd.
for C9H13NO2: C, 64.65; H, 7.84; N, 8.38. Found: C, 64.71; H, 7.79; N, 8.49.
N-(2-Phenylethyl)-amino-phenol (Table 6, Entry 4). Yellow liquid,
Rf ¼ 0.33 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over
12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 5.13 min, 97.27% purity. H NMR (CDCl3, 400 MHz): d 2.94–2.98 (m, 2H),
3.39–3.43 (m, 2H), 6.66–6.68 (m, 1H), 6.72–6.76 (m, 2H), 6.87–6.90 (m, 1H),
7.18–7.19 (m, 2H), 7.23–7.35 (m, 3H). 13C NMR (CDCl3, 100 MHz): d 35.75,
45.70, 112.76, 114.35, 117.95, 121.62, 126.38, 128.57, 128.76, 136.77, 139.42,
143.91. LCMS (UV): 214.2 (M þ Hþ). Anal. calcd. for C14H15NO: C, 78.84; H,
7.09; N, 6.57. Found: C, 78.90; H, 7.22; N, 6.53.

1912
S. NEOGI AND D. NASKAR
4-f2-(4-Methoxy-phenyl)-ethylaminog-phenol (Table 6, Entry 5). Yellow
liquid, Rf ¼ 0.64 (30% EtOAc–hexane); analytical HPLC: Symmetry C18
(4.6 ꢁ 75 mm, 5 mm particle size), mobile phase 0.1% TFA=CH3OH linear gradient
over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and UV at
1
Rt ¼ 3.85 min, 98.03% purity. H NMR (CDCl3, 400 MHz): d 2.84–2.87 (t, 2H),
3.30–3.34 (t, 2H), 3.81 (s, 3H), 6.54–6.56 (d, J ¼ 8.76, 2H), 6.69–6.71 (d, J ¼ 8.72,
2H), 6.86–6.88 (d, J ¼ 8.64, 2H), 7.13–7.15 (d, J ¼ 8.64, 2H). 13C NMR (CDCl3,
100 MHz): d 34.49, 46.29, 55.22, 113.95, 114.67, 116.13, 129.66, 131.22, 142.02,
147.81, 158.12. LCMS (UV): 244.2 (M þ Hþ). Anal. calcd. for C15H17NO2: C,
74.05; H, 7.04; N, 5.76. Found: C, 73.89; H, 7.21; N, 5.62.
3-f2-(4-Methoxy-phenyl)-ethylaminog-phenol (Table 6, Entry 6). Yellow
liquid, Rf ¼ 0.64 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18
(4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM NH4OAc=CH3OH linear
gradient over 12 min, with a flow of 0.8 mL=min, one peak detected by ELS and
1
UV at Rt ¼ 4.71 min, 98.21% purity. H NMR (CDCl3, 400 MHz): d 2.84–2.88 (t,
2H), 3.33–3.36 (t, 2H), 3.81 (s, 3H), 6.11–6.12 (s, 1H), 6.16–6.21 (m, 2H),
6.83–6.88 (m, 2H), 7.00–7.04 (m, 1H), 7.09–7.16 (m, 2H). 13C NMR (CDCl3,
100 MHz): d 34.42, 45.03, 55.22, 104.25, 106.03, 113.96, 129.59, 129.65, 130.14,
131.09, 149.62, 156.65, 158.16. LCMS (UV): 244.2 (M þ Hþ). Anal. calcd. for
C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C, 74.21; H, 7.11; N, 5.92.
3-Ethylamino-2-methyl-phenol (Table 6, Entry 7). Yellow liquid,
Rf ¼ 0.57 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 0.1% TFA=CH3OH linear gradient over 12 min,
with a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 1.22 min,
99.34% purity. 1H NMR (CDCl3, 400 MHz): d 1.29–1.33 (t, 3H), 2.05 (s, 1H),
3.18–3.23 (q, 2H), 4.81 (broad, 1H), 6.20–6.22 (d, J ¼ 7.96, 1H), 6.28–6.30 (d,
J ¼ 8.08, 1H), 6.96–7.00 (m, 1H). 13C NMR (CDCl3, 100 MHz): d 8.6, 15.00,
38.80, 103.25, 104.70, 107.55, 126.85, 147.74, 153.63. LCMS (UV): 152.2 (M þ Hþ).
Anal. calcd. for C9H13NO: C, 71.49; H, 8.67; N, 9.26. Found: C, 71.44; H, 8.74;
N, 9.09.
2-(3-Methyl-butylamino)-phenol (Table 6, Entry 8). Yellow liquid,
Rf ¼ 0.59 (30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm,
5 mm particle size), mobile phase 0.1% TFA=CH3OH linear gradient over 12 min,
with a flow of 0.8 ml=min, one peak detected by ELS and UV at Rt ¼ 3.59 min,
1
98.3% purity. H NMR (CDCl3, 400 MHz): d 0.95 (s, 3H), 0.97 (s, 3H), 1.53–1.58
(m, 2H), 1.72–1.77 (m, 1H), 3.13 (m, 2H), 6.62 (m, 1H), 6.69–6.71 (m, 2H), 6.87
(m, 1H). 13C NMR (CDCl3, 100 MHz): d 22.56, 25.94, 38.52, 42.51, 112.33,
114.21, 117.42, 121.51, 137.31, 143.62. LCMS (UV): 180.2 (M þ Hþ).
2-Pentylamino-phenol (Table 6, Entry 9). Yellow liquid, Rf ¼ 0.6 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 5.22 min, 98.85%
purity. 1H NMR (CDCl3, 400 MHz): d 0.89–0.94 (m, 3H), 1.33–1.43 (m, 4H),
1.65–1.66 (m, 2H), 3.12 (m, 2H), 6.64–6.71 (m, 3H), 6.87 (m, 1H). 13C NMR (CDCl3,

REDUCTIVE MONO-N-ALKYLATION
1913
100 MHz): d 14.08, 22.56, 29.23, 29.71, 44.34, 95.79, 103.96, 111.88, 117.23, 121.15,
137.53, 143.90. LCMS (UV): 180.2 (M þ Hþ).
4-Propylamino-phenol (Table 6, Entry 10). Yellow semisolid, Rf ¼ 0.65
(30% EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm par-
ticle size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with
a flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 3.08 min, 90.49%
purity. 1H NMR (CDCl3, 400 MHz): d 0.98–1.01 (m, 3H), 1.61–1.67 (m, 2H),
3.02–3.06 (m, 2H), 3.63 (broad, 1H), 6.56–6.58 (d, J ¼ 8.6, 2H), 6.69–6.72 (d,
J ¼ 8.6, 2H). 13C NMR (CDCl3, 100 MHz): d 11.63, 22.66, 47.18, 114.64, 116.18,
142.16, 147.90. LCMS (UV): 150.2 (M ꢀ Hþ).
6-Ethylamino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester
(Table 7, Entry 1). White solid, melting point ¼ 97.5–98.7 ꢂC, Rf ¼ 0.63 (30%
EtOAc–hexane); analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle
size), mobile phase 10 mM NH4OAc=CH3OH linear gradient over 12 min, with a
flow of 0.8 mL=min, one peak detected by ELS and UV at Rt ¼ 5.51 min, 97.32%
purity. 1H NMR (DMSO-d6, 400 MHz): d 1.12–1.17 (t, 3H), 1.50 (s, 9H),
2.85–2.89 (t, 2H), 2.95–3.01 (t, 2H), 3.81–3.85 (q, 2H), 5.43 (broad, 1H), 6.12–6.14
(d, J ¼ 8, 1H), 6.85–6.87 (d, J ¼ 8, 2H), 7.09 (s, 1H). 13C NMR (DMSO-d6,
100 MHz): d 14.87, 26.27, 28.53, 38.10, 48.38, 99.33, 106.63, 118.29, 125.23,
149.06, 152.17. LCMS (UV): 263.2 (M þ Hþ).
6-Isobutylamino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester
(Table 7, Entry 2). Yellow liquid, Rf ¼ 0.6 (30% EtOAc–hexane); analytical HPLC:
Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 0.1% TFA=
CH3OH linear gradient over 12 min, with a flow of 0.8 mL=min, one peak detected
by ELS and UV at Rt ¼ 4.99 min, 98.79% purity. 1H NMR (DMSO-d6, 400 MHz): d
0.90 (s, 3H), 0.92 (s, 3H), 1.50 (s, 9H), 1.79–1.86 (m, 1H), 2.75–2.78 (m, 2H),
2.84–2.88 (m, 2H), 3.81–3.85 (m, 2H), 5.54 (broad, 1H), 6.14–6.16 (d, J ¼ 8, 1H),
6.83–6.85 (d, J ¼ 8, 1H), 7.1 (s, 1H). 13C NMR (CDCl3, 100 MHz): d 20.06, 20.40,
26.44, 27.96, 28.41, 29.62, 48.26, 52.09, 100.19, 105.97, 124.75, 148.43, 152.57.
LCMS (UV): 291.2 (M þ Hþ). Anal. calcd. for C17H26N2O2: C, 70.31; H, 9.02; N,
9.65. Found: C, 70.48; H, 9.14; N, 9.67.
6-(3-Hydroxy-propylamino)-2,3-dihydro-indole-1-carboxylic acid tert-
butyl ester (Table 7, Entry 3). Yellow semisolid, Rf ¼ 0.35 (30% EtOAc–hexane);
analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase
10 mM NH4OAc=CH3OH linear gradient over 12 min, with a flow of 0.8 mL=min,
one peak detected by ELS and UV at Rt ¼ 4.95 min, 97.94% purity. 1H NMR
(DMSO-d6, 400 MHz): d 1.49 (s, 9H), 1.64–1.71 (m, 2H), 2.84–2.88 (m, 2H), 2.99
(m, 2H), 3.47–3.50 (m, 2H), 3.80–3.85 (m, 2H), 5.42 (broad, 1H), 6.12–6.14 (d,
J ¼ 8, 1H), 6.83–6.85 (d, J ¼ 8, 2H), 7.09 (s, 1H). 13C NMR (DMSO-d6,
100 MHz): d 11.92, 28.46, 32.14, 48.38, 59.12, 99.24, 125.28, 149.00, 152.27. LCMS
(UV): 293.2 (M þ Hþ). Anal. calcd. for C16H24N2O3: C, 65.73; H, 8.27; N, 9.58.
Found: C, 65.91; H, 8.35; N, 9.63.
6-(2-Ethoycarbonyl-ethylamino)-2,3-dihydro-indole-1-carboxylic acid tert-
butyl ester (Table 7, Entry 4). Yellow liquid, Rf ¼ 0.57 (30% EtOAc–hexane);

1914
S. NEOGI AND D. NASKAR
analytical HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase
0.1% TFA=CH3OH linear gradient over 12 min, with a flow of 0.8 mL=min, one peak
1
detected by ELS and UV at Rt ¼ 4.85 min, 94.21% purity. H NMR (DMSO-d6,
400 MHz): d 1.20–1.24 (t, 3H), 1.50 (s, 9H), 2.50–2.56 (m, 2H), 2.86–2.90 (m, 2H),
3.21–3.25 (m, 2H), 3.82–3.86 (m, 2H), 4.04–4.10 (m, 2H), 5.56 (broad, 1H),
6.14–6.16 (d, J ¼ 8, 1H), 6.86–6.88 (d, J ¼ 8, 1H), 7.1 (s, 1H). 13C NMR (DMSO-d6,
100 MHz): d 14.54, 28.50, 34.08, 48.38, 60.33, 79.63, 80.06, 99.47, 106.57, 118.84,
125.33, 148.48, 152.15, 169.72, 172.04. LCMS (UV): 335.2 (M þ Hþ). Anal. calcd.
for C18H26N2O4: C, 64.65; H, 7.84; N, 8.38. Found: C, 64.88; H, 8.02; N, 8.66.
6-Phenethylamino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester
(Table 7, Entry 5). Yellow liquid, Rf ¼ 0.58 (30% EtOAc–hexane); analytical
HPLC: Hypersil BDS C18 (4.6 ꢁ 50 mm, 5 mm particle size), mobile phase 10 mM
NH4OAc=CH3OH linear gradient over 12 min, with a flow of 0.8 mL=min, one peak
detected by ELS and UV at 98.86% purity. 1H NMR (CD3OD, 400 MHz): d 1.41 (s,
9H), 2.84–2.99 (m, 4H), 3.41–3.45 (m, 2H), 3.83–3.87 (m, 2H), 6.89–6.92 (m, 1H),
7.08–7.17 (m, 6H), 772–7.73 (m, 1H). 13C NMR (CD3OD, 100 MHz): d 28.57,
33.01, 54.07, 79.42, 82.47, 109.65, 117.21, 127.19, 128.21, 129.86, 134.63, 135.79,
137.45, 153.78, 162.13. LCMS (UV): 339.2 (M þ Hþ). Anal. calcd. for
C21H26N2O2: C, 74.52; H, 7.74; N, 8.28. Found: C, 74.57; H, 7.81; N, 8.37.
ACKNOWLEDGMENTS
The authors thank Dr. Ashis Baran Mandal and gratefully acknowledge Dr.
Goutam Das, COO, Syngene International Ltd., for his invaluable support.
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