Synthesis of spirofuranopyrimidine-piperidines

Article abstract of DOI:10.1016/j.tet.2012.04.033

A concise synthesis of spirofuranopyrimidines is described and relies on the addition of isopropyl 4-oxopiperidine-1-carboxylate to a pyrimidine dianion. The diol intermediate formed is subjected to cycloetherification conditions leading to an unprecedented heterocyclic template.

Full text of DOI:10.1016/j.tet.2012.04.033

Tetrahedron 68 (2012) 4596e4599
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of spirofuranopyrimidineepiperidines
*
Etzer Darout , Kim F. McClure, Vincent Mascitti
CVMED Chemistry, Pfizer Worldwide Research & Development, Groton Laboratories, Eastern Point Rd, Groton, CT 06340, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A concise synthesis of spirofuranopyrimidines is described and relies on the addition of isopropyl 4-
oxopiperidine-1-carboxylate to a pyrimidine dianion. The diol intermediate formed is subjected to cy-
cloetherification conditions leading to an unprecedented heterocyclic template.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 2 February 2012
Received in revised form 2 April 2012
Accepted 9 April 2012
Available online 14 April 2012
Keywords:
Spirocycle
Spiropiperidine
Spirofuran
C,O-dianion
1. Introduction
by 3. Previously, we described related attempts to make spirocyclic
analogs with an oxospiropyrazole core;8 however, the poor phar-
The application of benzo-spiropiperidines in drug discovery
programs is particularly prevalent for targets with endogenous
peptide ligands.1e4 While the circumstances for its use varies, the
ring system offers a defined way of arranging two contiguous rings
in an orthogonal manner, and in specific cases, this can be viewed as
a mimic for a phenylalanine residue.5 Our interest in these spi-
rocyclic systems stems from our goal of conformationally restricting
reported ligands of the G-protein coupled receptor 119 (GPR119)
(see Fig. 1).6,7 Our ongoing desire to better understand the struc-
tureeactivity relationship led us to target compounds generalized
macology observed with these compounds motivated us to preserve
the central pyrimidine from the model compounds 1 and 2 and to
evaluate other modes of spirocyclization. While related spiropiper-
idines have been applied to neuropeptide Y (NPY),1 melanocortin,2
and ghrelin,3,4,9,10 the incorporation of a fused pyrimidine would
require the development of a new synthesis. Herein we report the
synthesis of this heretofore unknown spirocyclic system via a two-
step C,O-dianion addition/cycloetherification sequence.
2. Results and discussions
We first envisioned the construction of the spirofused scaffold 4
via a strategy involving a late stage 5-exo cycloetherification from
hydroxymethyl pyrimidine precursor 5 via electrophilic activation
of the olefin11 (Scheme 1). In the cycloetherification of
g-hydroxy
olefins, 5-exo cyclization is generally preferred over the 6-endo
mode absent any overriding stereoelectonic and steric effects.12,13
Intermediate 5 would arise from a Suzuki cross-coupling reaction
of boronate 714 with a suitable chloropyrimidine derivative 6.
Readily available dichloropyrimidine 8 was identified as a suit-
able cross-coupling partner for this strategy. Suzuki cross-coupling
reaction of 8 with commercially available boronate ester 7 yielded
the desired pyrimidine derivative 9 in moderate yield. However,
attempts to activate the piperidine olefin to effect cyclo-
etherification to the spirofuran 10 were unsuccessful. Iodination2
and platinum-catalyzed hydroalkoxylation15 under both mild and
forcing conditions resulted in recovery of the alcohol 9 (Scheme 2).
Fig. 1. Spirofuranpyrimidineepiperidine as constrained GPR119 analogs.
* Corresponding author. E-mail address: Etzer.Darout@pfizer.com (E. Darout).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.033

E. Darout et al. / Tetrahedron 68 (2012) 4596e4599
4597
provided the expected alcohol 8 in moderate yield after column
chromatography, DIBALeH reduction cleanly provided the dichlor-
opyrimidine alcohol in very good yield following aqueous workup.
Iodination16 of 8, followed by silylation provided the silylether de-
rivative 17. The benzyl ether was introduced via an SNAr reaction and
subsequent desilylation of the resulting intermediate provided the
hydroxymethyl pyrimidine 18 in 39% overall yield.
Scheme 1. Retrosynthetic scheme to initial spirocyclization attempt.
Scheme 4. Reagents and conditions: (a) NaBH4, EtOH/THF, ꢀ15 ꢁC, 30 min, 40%; (b)
DIBALeH, THF/toluene, ꢀ78 ꢁC, 45 min, 81%; (c) Hydriodic acid (57% aq solution), room
temperature, 1 h, 98%; (d) TBSeCl, Imid., DMF, room temperature, 15 h, 81%; (e) sodium
benzyloxide, BnOH, THF, 0 ꢁC to room temperature, 14 h; (f) TBAF, THF, 0 ꢁC to room
temperature, 15 h, 61% (two steps).
With 18 in hand, we began to investigate its utility as a C,O-
dianion nucleophile (see Table 1). Treatment of 18 with 0.9 equiv of
Turbo Grignard (isopropylmagnesium chloride complexed with
lithium chloride) at ꢀ78 ꢁC for 30 min, followed by a methanol
quench, resulted in unchanged starting material by TLC and UPLC
analysis. However when 18 was treated at ꢀ40 ꢁCwith a stoichio-
metric amount of Grignard reagent, there was evidence of the des-
iodo product by both TLC and UPLC. This suggests that at higher
temperatures, metalehalogen exchange competes with deproto-
nation.17,18 To avoid using a large excess of Turbo Grignard, meth-
ylmagnesium bromide was first used for the deprotonation of 18.
Turbo Grignard was then used to accomplish the metaleiodine
exchange. Results from the various conditions explored are exem-
plified in Table 1. Treatment of the C,O-dianion of pyrimidine 18,
formed from deprotonation and subsequent metaleiodine
Scheme 2. Reagents and conditions: (a) Pd(PPh3)4, 2 M Na2CO3, 1,4-dioxane, 140 ꢁC,
microwave, 40%.
Given, these results an alternative approach was explored to arrive
at the desired spirocyclic core.
The synthesis of spiro[isobenzofuran-1(3H),40-piperidines] have
been previously reported and were accessed via carboxylate dia-
nion addition to piperidinones.9 The C,O-dianion described was
derived from 2-bromobenzoic acid. The dianion strategy increases
the ease of generating and controlling the dilithio species and
eliminates the need for a hydroxymethyl protecting group. Since
this approach offered elements of practicality, we decided to ex-
plore a C,O-dianion strategy in the unprecedented context of
a substituted 4-iodo-5-hydroxymethyl pyrimidine 11 as precursor
(Scheme 3). We hypothesized that generation of dianion 12 from 11,
followed by nucleophilic addition of 12 to 13 would provide 14,
which upon cycloetherification would lead to the desired spi-
ropyrimidine core 15.
Table 1
Results of reactions of pyrimidine derivative 13 with carbonyl electrophiles
Nucleophile
Electrophile
Product
Yield (%)
75
18
18
18
70
57
Scheme 3. Dianion addition precursors and spirofused derivatives.
As shown in Scheme 4, an efficient route to gram quantities of
hydroxymethyl pyrimidine 18 was achieved in five steps and in-
cluded only one chromatographic purification step. The sequence
begins with reduction of commerciallyavailable dichloropyrimidine
aldehyde 16. While treatment of 16 with sodium borohydride
Conditions: (a) MeMgBr, THF, ꢀ50 ꢁC, 15e25 min; then i-PrMgCl$LiCl, ꢀ50 ꢁC to
0
ꢁC; then addition of carbonyl electrophile.

4598
E. Darout et al. / Tetrahedron 68 (2012) 4596e4599
exchange, with excess N,N-dimethylformamide, gave the fused bi-
cyclic hemiacetal derivative 22 in good yield. Likewise, addition of
nicotinaldehyde to a solution of the dianion gave the bicyclic diol 24
in good yield. A true test of this methodology involved the reaction
of the dianion with oxopiperidine 25, which gratifyingly resulted in
the desired diol 26 in moderate yield. After exploring various op-
tions, cycloetherification of diol 26 was successfully executed in
a one-pot tosylation, nucleophilic displacement in good yield
(Scheme 5).19
1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate
(82 mg, 0.29 mmol), 1.4-dioxane (1.40 mL), and 2 M Na2CO3
(0.35 mL). The heterogeneous mixture was degassed by bubbling
nitrogen through the mixture. After 10 min, Pd(PPh3)4 (23 mg,
0.02 mmol) was added and the reaction mixture was degassed for
another 5 min. The reaction vessel was capped and irradiated at
140 ꢁC in the microwave for 30 min. After cooling, the vial was
vented to relieve the pressure. The mixture was concentrated to
dryness and purified by flash column chromatography with an
isocratic elution of 40% EtOAc/heptane to give 35 mg (40%) of the
title compound as a clear oil. 1H NMR (500 MHz, CDCl3)
d ppm 1.28
(d, J¼6.35 Hz, 6H), 2.59e2.73 (m, 3H), 3.70, (appt t, J¼5.60 Hz, 2H),
4.18, (appt d, J¼2.45 Hz, 2H), 4.79, (d, J¼5.60 Hz, 2H), 4.97, (sep,
J¼6.35 Hz, 1H), 6.33, (br s, 1H), 8.86 (s, 1H); 13C NMR (125 MHz,
CDCl3)
d ppm 21.3, 26.6, 30.9, 42.4, 58.2, 67.9, 127.5, 154.2, 156.0,
162.1, 167.9, 180.5; HRMS (ESI) MHþ, found 311.1105. C14H18ClN3O3
requires 311.1037.
Scheme 5. Reagents and conditions: (a) NaHMDS (2 equiv), THF, 0 ꢁC; TsCl 30 min,
74%.
In conclusion, the expedient synthesis of pyrimidine 18 was
successfully achieved in five steps, and several electrophiles were
used to establish its utility as a C,O-dianion precursor. The forma-
tion of the dianion was achieved with a two-base system to allow
deprotonation prior to metaleiodine exchange. This strategy effi-
ciently generated the dianion and avoided the use of a protecting
group on the pyrimidine C-5-hydroxymethyl. Subsequent addition
of electrophiles to the in situ generated dianion led to the synthesis
3.1.3. (4,6-Diiodopyrimidin-5-yl)methanol. Hydriodic acid (250 mL
of 57% aq solution) was added to (4,6-dichloropyrimidin-5-yl)
methanol (20.5 g, 0.12 mol) at ambient temperature. The mixture
was stirred for 1 h during which time a yellow solid precipitated out
of the orange-brown solution. The mixture was diluted with water,
cooled to 0 ꢁC, and filtered. The solid was collected and dried to give
40 g (98%) of the title compound as a yellow solid, mp 98e103 ꢁC.1H
NMR (500 MHz, CDCl3) d ppm 2.50 (s, 1H), 4.69 (s, 2H), 8.36 (s, 1H);
13C NMR (125 MHz, CDCl3)
d ppm 70.2, 135.7, 143.3, 157.9; HRMS
of
a complex spirofuranopyrimidineepiperidine core. To our
(ESI) MHþ, found 362.8492. C5H4I2N2O requires 361.8413.
knowledge, this is the first example of a C,O-dianion strategy
wherein hydroxypyrimidine is used as a nucleophile. This meth-
odology has led to a rapid, practical, and scalable synthesis of the
spiropyrimidine piperidine motif that can potentially be applied to
other medicinal chemistry programs.
3.1.4. 5-((tert-Butyldimethylsilyloxy)methyl)-4,6-diiodopyrimidine
(17). To a mixture of (4,6-diiodopyrimidin-5-yl)methanol (40.0 g,
0.11 mol) in DMF (553 mL) were added TBSeCl (38 g, 0.25 mol) and
imidazole (19 g, 0.28 mmol). After 15 h, the reaction mixture was
concentrated under reduced pressure to remove all of the DMF. The
resulting viscous amber oil was dissolved in DMSO (50 mL) and
added to a 500 mL separatory funnel. The material was extracted
from DMSO with heptane (200 mLꢂ5). The combined heptane
layers were dried over MgSO4 and filtered. The filtrate was con-
centrated under reduced pressure to give 42.4 g (81%) of the title
compound as a white solid, mp 70e73 ꢁC. 1H NMR (500 MHz,
3. Experimental section
3.1. General
3.1.1. (4,6-Dichloropyrimidin-5-yl)methanol (8). Procedure A: To
a
solution of 4,6-dichloropyrimidine-5-carbaldehyde (500 mg,
2.82 mmol) in 1:1 THF/EtOH (23 mL) at ꢀ15 ꢁC (MeOH/ice) was
added NaBH4. After 30 min, the reaction was once again cooled to
ꢀ15 ꢁC, followed by dropwise addition of 2 M HCl in diethyl ether
until all the bubbling had ceased. The reaction mixture was con-
centrated and adsorbed onto silica. The solid residue was loaded
and purified by flash column chromatography (ISCO combiflash)
using a gradient elution of 0e4% MeOH/DCM to give 240 mg (47%)
of the title compound as a white solid.
CDCl3)
NMR (125 MHz, CDCl3)
d C
ppm 0.23 (s, 6H), 0.98 (s, 9H), 4.93 (s, 2H), 8.31 (s, 1H); 13
d
ppm 0.00, 23.7, 31.0, 76.8, 138.3, 147.5,
161.8; HRMS (ESI) MHþ, found 475.9357. C11H18I2N2OSi requires
475.9278.
3.1.5. (4-(Benzyloxy)-6-iodopyrimidin-5-yl)methanol (18). To a solu-
tion of 5-((tert-butyldimethylsilyloxy)methyl)-4,6-diiodopyrimidine
(40.8 g, 85.8 mmol) in THF (430 mL) was added 1 M benzyloxide in
benzyl alcohol (prepared from 1.97 g of sodium and benzyl alcohol
85 mL) at 0 ꢁC. The reaction mixture was allowed to stir for 14 h.
Most of the benzyl alcohol was removed by distillation under high
vacuum with a bath temperature 80e100 ꢁC. The crude residue was
dissolved in THF (200 mL) and TBAF (129 mL of 1 M TBAF in THF)
was added at 0 ꢁC. After 5 min, the ice bath was removed and the
reaction mixture was allowed to stir for 15 h. The reaction mixture
was concentrated and purified by flash column chromatography
using a 330 g ISCO column with an eluant of 40% EtOAc/heptane to
give 18 g (61%) of the title compound as a white solid, mp 89e95 ꢁC.
Procedure B: To
a solution of 4,6-dichloropyrimidine-5-
carbaldehyde (4000 mg, 22.6 mmol) in THF (100 mL) at ꢀ78 ꢁC
was added dropwise a solution of DIBAL (15.8 mL of 1.5 M solution
in toluene) over 15 min. After an additional 30 min at ꢀ78 ꢁC,
a saturated aqueous solution of Rochelle’s salt (50 mL) was added
and the dry ice/acetone bath was removed. The reaction mixture
was allowed to warm to room temperature and stirred for 14 h. At
this point, the layers were separated and the organic phase was
dried over MgSO4, filtered, and the filtrate concentrated under re-
duced pressure to give 3.25 g (81%) of the title compound as a white
solid, mp 88e90 ꢁC. 1H NMR (500 MHz, CDCl3)
d
ppm 2.36 (br s,
ppm
1H), 4.97 (s, 2H), 8.74 (s, 1H); 13C NMR (125 MHz, CDCl3)
d
1H NMR (500 MHz, CDCl3)
2H), 7.26e7.45 (m, 5H), 8.38 (s, 1H); 13C NMR (125 MHz, CDCl3)
d ppm 2.23 (br s, 1H), 4.78 (s, 2H), 5.50 (s,
59.6, 130.8, 157.6, 162.7; HRMS (ESI) MHþ, found 178.9775.
C5H4Cl2N2O requires 177.9701.
d
ppm 63.2, 69.5, 125.8, 128.5, 129.0, 133.8, 135.6, 157.3, 166.0; HRMS
(ESI) MHþ, found 341.9916. C12H11IN2O2 requires 341.9865.
3.1.2. Isopropyl 4-(6-chloro-5-(hydroxymethyl)pyrimidin-4-yl)-5,6-
dihydropyridine-1(2H)-carboxylate (9). To a 5 mL microwave vial
equipped with a stir bar were added (4,6-dichloropyrimidin-5-yl)
methanol (50 mg, 0.28 mmol), isopropyl 4-(4,4,5,5-tetramethyl-
3.1.6. 4-(Benzyloxy)-5,7-dihydrofuro[3,4-d]pyrimidin-7-ol (22). To
a
solution of (4-(benzyloxy)-6-iodopyrimidin-5-yl)methanol
(300 mg, 0.877 mmol) in THF (4.38 mL) at ꢀ50 ꢁC was added of 3 M

E. Darout et al. / Tetrahedron 68 (2012) 4596e4599
4599
methylmagnesium bromide (0.292 mL, 0.877 mmol, 3 M in diethyl
ether). After 15 min, isopropylmagnesium chloride/lithium chlo-
ride (1.36 mL, 1.8 mmol, 1.3 M solution in THF) was added. After
5 min, the CH3CN bath was removed and replaced with an ice bath.
The reaction was allowed to stir until metalehalogen exchange was
complete by TLC analysis (indicated by hydro-deiodination product
(50% EtOAc/heptane)). DMF (1 mL, 10 mmol) was added and the
reaction mixture stirred for 16 h. The reaction was quenched with
satd NH4Cl and the layers were separated. The aqueous layer was
extracted 3ꢂ with EtOAc. The combined organic layers were
washed with brine, dried over Na2SO4, filtered, and the filtrate was
concentrated. Purification of the crude by flash column chroma-
tography with 30% EtOAc/heptane gave the title compound
155.7, 168.6, 170.9; HRMS (ESI) MHþ, found 401.2004. C21H27N3O5
requires 401.1951.
3.1.9. Isopropyl 4-(benzyloxy)-5H-spiro[furo[3,4-d]pyrimidine-7,40-pi-
peridine]-10-carboxylate (27). To a solution of isopropyl 4-(6-(ben-
zyloxy)-5-(hydroxymethyl)pyrimidin-4-yl)-4-hydroxypiperidine-1-
carboxylate (22 mg, 0.055 mmol) in THF (0.5 mL) at 0 ꢁC was added
NaHMDS (0.121 mL, 0.121 mmol of 1 M solution in THF). After
stirring for 5 min, a solution of TsCl (13 mg, 0.0660 mmol) in THF
(0.5 mL) was added dropwise. After 20 min, the reaction mixture
was quenched via the addition of satd NH4Cl and brine followed.
The heterogeneous mixture was poured into a separatory funnel
and extracted with DCM (3ꢂ2 mL). The combined DCM layers were
dried over MgSO4, filtered, and the filtrate concentrated. Purifica-
tion using a 4 g RediSep column with 45% EtOAc/heptane as an
eluant gave 80 mg (74%) of the title compound as a clear oil. 1H
(160 mg (75%)) as a white foam. 1H NMR (500 MHz, CDCl3)
d ppm
5.03 (d, J¼13.5 Hz, 1H), 5.24 (dd, J¼2.7, 13.5 Hz, 1H), 5.54 (s, 2H),
6.51 (d, J¼2.45 Hz, 1H), 7.35e7.46 (m, 5H), 8.81 (s, 1H); 13C NMR
(125 MHz, CDCl3)
d
ppm 68.4, 68.9, 99.2, 117.5, 128.6, 128.8, 128.9,
NMR (500 MHz, CDCl3)
d
ppm; 1.27 (d, J¼6.50 Hz, 6H), 1.64e1.68
135.7, 158.9, 164.8, 168.7; HRMS (ESI) MHþ, found 244.0905.
C13H12N2O3 requires 244.0848.
(m, 2H), 2.00 (dt, J¼4.5, 13.0 Hz, 2H), 3.20e3.34 (m, 2H), 4.01e4.20
(m, 2H), 4.95 (sept, J¼6.0 Hz, 1H), 5.05 (s, 21H), 5.51 (s, 2H),
7.33e7.47 (m, 5H), 8.73 (s, 1H); 13C NMR (125 MHz, CDCl3)
d ppm
3.1.7. (6-(Benzyloxy)-5-(hydroxymethyl)pyrimidin-4-yl)(pyridin-3-
yl)methanol (24). To a solution of 4-(benzyloxy)-6-iodopyrimidin-
5-yl)methanol (300 mg, 0.877 mmol) in THF (4.40 mL) at ꢀ50 ꢁC
was added methylmagnesium bromide (0.292 mL, 0.877 mmol of
3 M solution in diethyl ether. After 20 min, isopropylmagnesium
chloride/lithium chloride (1.36 mL, 1.8 mmol of 1.3 M solution in
THF) was added. After 5 min, the CH3CN bath was removed and
replaced with an ice bath. The reaction mixture was allowed to stir
for 30 min. At this point a mixture of nicotinaldehyde (188 mg,
1.75 mmol) in THF (1 mL) was added dropwise followed by a 0.5 mL
rinse. The solution was allowed to stir overnight. The reaction was
quenched with satd NH4Cl and the layers were separated. The
aqueous layer was extracted 3ꢂ with EtOAc. The combined organic
layers were washed with brine, dried over Na2SO4, filtered, and
concentrated. Purification of the crude with EtOAc as the eluant
gave the title compound 200 mg (70%) as a clear oil. 1H NMR
22.5, 34.4, 40.2, 67.2, 68.5, 68.9, 84.3 115.7, 128.6, 128.7, 128.9, 136.1,
155.5, 158.8, 164.2, 173.6. HRMS (ESI) MHþ, found 383.1902.
C21H25N3O4 requires 383.1845.
Acknowledgements
I’d like to thank Christian Perreault for the melting point
analysis of compound 18. I’d also like to thank Dr. Benjamin D.
Stevens and Dr. Elnaz Menhaji-Klotz for their constructive com-
ments and suggestions.
References and notes
1. Takahashi, T.; Haga, Y.; Sakamoto, T.; Moriya, M.; Okamoto, O.; Nonoshita, K.;
Shibata, T.; Suga, T.; Takahashi, H.; Hirohashi, T.; Sakuraba, A.; Gomori, A.;
Iwaasa, H.; Ohe, T.; Ishihara, A.; Ishii, Y.; Kanatani, A.; Fukami, T. Bioorg. Med.
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Tang, R.; Tamvakopoulos, C.; Peng, Q.; Chen, H. Y.; Chen, A. S.; Martin, W. J.;
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(500 MHz, CDCl3)
d
ppm 4.58e4.70 (m, 2H), 5.48 (dd, J¼12.2,
18.8 Hz, 2H), 6.10 (s, 1H), 7.20e7.45 (m, 6H), 7.73 (d, J¼7.85 Hz, 1H),
8.43 (appt d, J¼3.70 Hz, 1H), 8.57 (s, 1H), 8.75 (s, 1H); 13C NMR
(125 MHz, CDCl3)
d ppm 53.6, 67.9, 69.3, 116.2, 122.7, 127.1, 127.4,
127.6, 134.1, 134.7, 136.8, 147.2, 147.7, 155.5, 165.4, 166.6; HRMS (ESI)
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zyloxy)-6-iodopyrimidin-5-yl)methanol (300 mg, 0.877 mmol) in
THF (4.4 mL) at ꢀ50 ꢁC was added methylmagnesium bromide
(0.292 mL, 0.877 mmol of 3 M) solution in diethyl ether. After
25 min, isopropylmagnesium chloride/lithium chloride (1.36 mL,
1.8 mmol of 1.3 M solution in THF) was added. After 5 min, the
CH3CN bath was removed and replaced with an ice bath. The re-
action mixture was allowed to stir until consumption of the iodide
was observed by TLC analysis (30% EtOAc/heptane). At this point
a mixture of isopropyl 4-oxopiperidine-1-carboxylate (487 mg,
2.63 mmol) in THF (1 mL) was added dropwise followed by a 0.5 mL
rinse. The solution was allowed to stir overnight. The reaction was
quenched with satd NH4Cl and the layers were separated. The
aqueous layer was extracted 3ꢂ with EtOAc. The combined organic
layers were washed with brine, dried over Na2SO4, filtered, and the
filtrate concentrated. Purification of the crude with 30% EtOAc/
heptane as the eluant gave the title compound as a clear oil 200 mg
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(57%). 1H NMR (500 MHz, CDCl3)
d
ppm 1.25 (d, J¼6.35 Hz, 6H), 1.66
(d, J¼13.2 Hz, 2H), 2.24e2.29 (m, 2H), 3.15e3.25 (m, 3H), 4.00e4.13
(m, 2H), 4.86e4.95 (m, 3H), 5.11 (br s, 1H), 5.48 (s, 2H), 7.33e7.46
(m, 5H), 8.66 (s, 1H); 13C NMR (125 MHz, CDCl3)
d
ppm 22.5, 37.0,
40.0, 55.5, 68.9, 69.1, 74.1, 117.6, 128.3, 128.6, 128.9, 136.2, 155.5,