Convenient synthetic methods to C2 symmetric 3,4-diphenylpyrrolidines

Article abstract of DOI:10.1055/s-2000-6404

Convenient methods of synthesis of racemic and optically pure 3,4- diphenylpyrrolidine derivatives, involving oxidative coupling of ethyl phenylacetate using TiCl₄/Et₃N and reduction of the dl-2,3-diphenylsuccinic acid or the corresponding cyclic imide with NaBH₄/I₂ reagent in crucial steps, are described.

Full text of DOI:10.1055/s-2000-6404

PAPER
703
Convenient Synthetic Methods to C2 Symmetric 3,4-Diphenylpyrrolidines
Vutukuri Dharma Rao, Mariappan Periasamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, India
Fax +91-040-3010120; E-mail: mpsc@uohyd.ernet.in
Received 23 December 1999; revised 21 January 2000
Ph
Ph
TiCl4/Et3N
KOH
Abstract: Convenient methods of synthesis of racemic and optical-
ly pure 3,4-diphenylpyrrolidine derivatives, involving oxidative
coupling of ethyl phenylacetate using TiCl4/Et3N and reduction of
the dl-2,3-diphenylsuccinic acid or the corresponding cyclic imide
with NaBH4/I2 reagent in crucial steps, are described.
PhCH2COOEt
CH2Cl2, - 45oC
75%
EtOH:H2O/1:1
reflux, 6h
EtOOC
COOEt
dl-3
92%
Ph
O
Ph
Ph
Ph
COOH
RNH2
NaBH4/I2
Key words: chiral dicarboxylic acid, diol, cyclic imide, 3,4-diphe-
nylpyrrolidine, oxidative coupling, reductions, amines
220oC, 1.5h
THF, reflux , 6h
HOOC
O
N
R
dl-4
5a, R = (R)- (+)-CH(CH3)Ph (85%)
The chiral 3,4-diphenylpyrrolidine system 1 is a syntheti-
cally useful ligand in asymmetric dihydroxylation of ole-
fins to obtain the corresponding diols in high
enantioselectivity using OsO4,1-4 and for asymmetric ad-
dition of Grignard reagents to benzaldehyde.5 The synthe-
sis of diamine 1 was reported by Tomioka et al.6 During
our investigations on the use of chiral amine borane com-
plexes,7-9 we were looking for convenient methods of
synthesis of the 3,4-diphenylpyrrolidine derivatives 2. We
wish to report such methods of synthesis of 2, using readi-
ly accessible, inexpensive reagents.
5b, R = CH2Ph
5c, R = 2-MeOC6H4
(90%)
(80%)
Ph
Ph
N
R
6a, R = (R)- (+)-CH(CH3)Ph
6b, R = CH2Ph
6c, R = 2-MeOC6H4
(75%)
(76%)
(75%)
Scheme 1
Ph
Ph
the corresponding ditosylate 8 to obtain the pyrrolidine
systems was developed (Scheme 2). The amines were ob-
tained in excellent yields (80-95%) from the ditosylate 8
in this way.
Ar
Ar
Ar
Ar
N
N
N
R
2
1, Ar = Ph , 3,5-Xylyl
Ph
Ph
Ph
Ph
TsCl/Py
85%
NaBH4/I2
THF, r.t, 12h
reflux, 4h
HOOC
COOH
HOH2C
CH2OH
The sequence of reactions outlined in Scheme 1 was fol-
lowed for the synthesis via the reduction of the corre-
sponding cyclic imides 5 using NaBH4/I2.
90%
dl-7
dl-4
dl-Diethyl 2,3-diphenylsuccinate (dl-3) was prepared
from ethyl phenylacetate using TiCl4/Et3N in CH2Cl2
at -45 ∞C.10 It was saponified using KOH in EtOH/H2O
(1:1) to give the dl-2,3-diphenylsuccinic acid (dl-4),
which was condensed with amines to form the cyclic imi-
des 5. The cyclic imides were reduced following the sim-
ple, easy to handle NaBH4/I2 reagent system developed in
this laboratory,11-13 to give the required amines 6 in 75-
76% yield. In the case of 6a, the diastereomeric mixture
was separated by column chromatography on silica gel us-
ing hexane as eluent.
Ph
Ph
Ph
TsOH2C
Ph
RNH2 (excess)
120oC, 2h
N
R
CH2OTs
dl-8
6a, R = (R)-(+)-CH(CH3)Ph (88%)
6b, R = CH2Ph
6d, R = CH2CH2OH
6e, R = CH2CH2OCH3
(83%)
(95%)
(90%)
Scheme 2
We have observed that the condensation of 2,3-diphenyl-
succinic acid (4) did not proceed well for certain amine
derivatives with sensitive functional groups (e.g. 6d). So,
an alternative procedure involving the reduction of the di-
carboxylic acid with NaBH4/I2, followed by cyclization of
We have also employed these procedures for the prepara-
tion of a chiral 3,4-diphenylpyrrolidine system (Scheme
3). The dl-2,3-diphenylsuccinic acid (dl-4) was resolved
using (S)-proline following a slightly modified proce-
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704
V. D. Rao, M. Periasamy
PAPER
IR (KBr): n = 1718, 1602 cm-1.
1H NMR: d = 1.2 (t, 6 H, J = 16 Hz), 3.9-4.15 (m, 4 H), 4.2 (s, 2 H),
dure.14 The enantiomerically pure (2S,3S)-(+)-2,3-diphe-
nylsuccinic acid [(2S,3S)-4a] prepared in this way was
reduced with NaBH4/I2 reagent to obtain the correspond- 6.9-7.1 (m, 4 H), 7.1-7.2 (m, 6 H).
13C NMR: d = 14.0, 55.0, 61.1, 127.3, 128.4, 129.0, 135.9, 173.1.
ing chiral diol (2S,3S)-(+)-7a in 86% yield. The corre-
sponding optically pure ditosylate (2S,3S)-8a was
prepared using TsCl/pyridine. Cyclization of the ditosy-
late (2S,3S)-(+)-8a with 2-methoxyethylamine proceeded
to give the corresponding chiral derivative (2S,3S)-(+)-6e
in 90% yield (Scheme 3).
The diester 3 (6.5 g, 20 mmol) prepared as above was taken in aq
EtOH (H2O/EtOH, 1:1) and excess KOH (5.6 g) was added. The
contents were refluxed for 6 h. EtOH was removed under reduced
pressure and the contents were cooled and acidified with 3 N HCl.
The dl-2,3-diphenylsuccinic acid (4) was separated by filtration,
dried and purified by recrystallization form H2O; yield: 5 g (92%);
mp 182 °C solidified and remelted at 220 °C (Lit.15,16 mp 183 °C so-
lidified and remelted at 220-221 °C).
Ph
Ph
Ph
Ph
NaBH4/I2
(S)-Proline
IR (KBr): n = 1709, 1601 cm-1.
THF, r.t, 12h
reflux, 4h
Methanol
HOOC
COOH
HOOC
COOH
Cyclic Imides 5a-c; N-(a-Methylbenzyl)-3,4-diphenylpyrroli-
din-2,5-dione (5a); Typical Procedure
86%
dl-4
(2S, 3S)-4a
A mixture of dl-4 (5.4 g, 20 mmol) and (R)-(+)-a-methylbenzy-
lamine (2.4 g, 20 mmol) was heated neat at 220 °C for 1.5 h. The
mixture was cooled and the yellow cake formed was dissolved in
CHCl3. The CHCl3 phase was washed with brine and dried
(MgSO4). Evaporation of the solvent gave a yellow solid which was
purified by column chromatography over silica gel using hexane/
EtOAc (95:5) as eluent; yield: 6 g (85%); mp 87-88 °C.
Ph
TsOH2C
(2S, 3S)-8a
Ph
Ph
Ph
NH2CH2CH2OCH3
TsCl/Py
84%
120°C, 2h
90%
CH2OTs
HOH2C
CH2OH
(2S, 3S)-7a
Ph
IR (KBr): n = 1774, 1699 cm-1.
Ph
1H NMR: d = 1.9 (2 d, 3 H, J = 10 Hz), 4.0 (d, 2 H, J = 10 Hz), 5.5
(m, 1 H), 7.0-7.6 (m, 15 H).
N
13C NMR: d = 15.0, 15.5, 49.4, 49.7, 53.8, 126.4, 126.7, 127.3,
128.0, 135.6, 138.2, 138.4, 175.2. (more signals due to the presence
of diastereomers).
CH2CH2OCH3
(2S, 3S)-6e
Anal. cald for C24H21NO2: C, 81.12; H, 5.91; N, 3.94; found: C,
81.22; H, 5.97; N, 4.1.
Scheme 3
The derivatives 5b and 5c were also prepared following the above
procedure.
In conclusion, the convenient synthetic procedures de-
scribed here for the preparation of ( ) and chiral 3,4-
diphenylpyrrolidine system should facilitate the syntheses
and applications of these derivatives.
5b
Yield: 6.1 g (90%); mp 83-84 °C.
IR (KBr): n = 1782, 1707 cm-1.
1H NMR: d = 4.2 (s, 2 H), 4.9 (d, 2 H, J = 10 Hz), 7.1-7.6 (m, 15 H).
13C NMR: d = 43.0, 55.4, 127.7, 128.0, 128.8, 129.2, 136.5, 176;
TiCl4 (Spectrochem, India), (R)-(+)-a-methylbenzylamine (99.8%)
(Fluka, Switzerland), and 2-methoxyethylamine (Lancaster, United
Kingdom) were used as such. Ethyl phenylacetate and the amines
used are commercial samples. CH2Cl2 was distilled over P2O5 and
then CaH2, and dried over molecular sieves 4Å. THF freshly dis-
tilled over benzophenone-sodium was used. IR spectra were record-
ed on JASCO-FT-IR model 5300 spectrometer with polystyrene as
Anal. calcd for C23H19NO2: C, 80.93; H, 5.57; N, 4.10; found: C,
81.03; H, 5.62; N, 4.18.
5c
Yield: 5.7 g (80%); mp 127-128 °C.
IR (KBr): n = 1780, 1709, 1601 cm-1.
1H NMR: d = 3.8 (s, 3 H), 4.2 (s, 2 H), 7.0-7.6 (m, 14 H).
13C NMR: d = 56.0, 56.3, 56.9, 112.3, 121.0, 127.6, 127.8, 128.0,
129.2, 129.3, 130.9, 137.0, 137.6, 154.8, 175.7.
1
reference. H NMR (200 MHz) and 13C NMR (50 MHz) spectra
were recorded in CDCl3 on Bruker AC-200 spectrometer using
TMS as internal stanarad. Elemental analyses were recorded on Per-
kin-Elmer 240-CHN analyzer. Optical rotations were measured
with an Autopol II-automatic polarimeter at 27 °C. For TLC analy-
sis, plates coated with silica gel were run in hexane/EtOAc mixture
and spots were developed in an I2 chamber. For column chromato-
graphic separations under gravity, column grade silica gel (100-
200 mesh) was employed.
Anal. calcd for C23H19NO3: C, 77.31; H, 5.32; N, 3.92; found: C,
77.36; H, 5.36; N, 3.95.
N-Substituted 3,4-Diphenylpyrrolidines 6a-c; N-(a-Methyl-
benzyl)-3,4-diphenylpyrrolidine (6a); Typical Procedure
NaBH4 (2.2 g, 58 mmol) was taken in anhyd THF (120 mL) under
N2 in a two-necked septum capped round-bottom flask. I2 (6.1 g,
24 mmol) dissolved in anhyd THF (75 mL) was added under N2 at
0 °C during 2.5 h. The diborane generated in situ was quantitatively
trapped as BH3∑THF complex. To this reagent was added the imide
5a (3.55 g, 10 mmol) dissolved in anhyd THF (30 mL) through a
cannula and the mixture was refluxed for 6 h. The contents were
cooled to 0 °C and the excess hydride was carefully destroyed with
3 N HCl (10 mL). After the gas evolution had ceased, it was neutral-
N-Substituted 3,4-Diphenylpyrrolidines (Scheme 1)
dl-2,3-Diphenylsuccinic Acid (dl-4)
Ethyl phenylacetate was converted to the diester 3 by following the
procedure described for the corresponding methyl ester.10 The prod-
uct was purified by column chromatography (hexane/EtOAc, 98:2)
to give the dl-2,3-diphenylsuccinic acid diethyl ester (dl-3); yield:
6.1 g (75%); mp 82 °C (Lit.15,16 mp 82-83.5 °C).
Synthesis 2000, No. 5, 703–706 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Convenient Synthetic Methods to C2 Symmetric 3,4-Diphenylpyrrolidines
705
ized using 3 N NaOH (20 mL). The organic layer was separated
and the aqueous layer was extracted with Et2O (3 × 20 mL). The
combined organic extracts were washed with H2O (15 mL), brine
(20 mL) and dried (MgSO4). The solvent was evaporated and the
residue was taken in anhyd Et2O. BF3∑OEt2 was added followed by
3 N NaOH (25 mL) solution and the amine was extracted into Et2O
(3 × 20 mL). The combined organic extracts were washed with
brine and dried (MgSO4). Evaporation of the solvent afforded the
diastereomeric mixture of amines which was purified by column
chromatography on silica gel using hexane as eluent; yield: 2.45 g
(75%). The diastereomer eluted first was obtained in pure form after
column chromatography separation using hexane as eluent; yield:
0.45g; [a]D27 +72 (c = 1, CHCl3).
IR (neat): n = 3061, 1601 cm-1.
1H NMR: d = 1.7 (d, 3 H, J = 16 Hz), 3.0-3.7 (m, 7 H), 7.3-7.7 (m,
15 H).
13C NMR: d = 23.4, 53.2, 61.7, 66.0, 126.5, 127.2, 127.4, 127.5,
127.7, 128.6, 144.2, 145.8
silica gel column using hexane/EtOAc (80:20) as eluent; yield: 2.17
g (90%); mp 100-101 °C
IR (KBr): n = 3269, 3060, 1601 cm-1.
1H NMR: d = 2.3 (br s, 2 H), 3.25 (m, 2 H), 4.0 (m, 4 H), 6.9-7.0
(m, 4 H), 7.0-7.2 (m, 6 H).
13C NMR: d = 51.03, 65.5, 126.5, 128.1, 128.6, 140.6.
dl-2,3-Diphenylbutane-1,4-di(p-toluenesulfonate) (dl-8)
Anhyd pyridine (30 mL, 380 mmol) was added slowly to a mixture
of diol 7 (4.84 g, 20 mmol) and p-toluenesulfonyl chloride (15.2 g,
80 mmol) at -15 °C. The mixture was stirred at -10 °C for 4 h and
then kept at 0 °C for 24 h. After pouring into ice-water, the resulting
oil solidified in 0.5 h. It was filtered and washed consecutively with
H2O, 2% HCl, 2% aq NaOH solution , and H2O. Yield of the crude
8 was 8.94 g (85%). It was further purified by recrystallisation from
benzene/hexane; mp 138-140 °C.
IR (KBr): n = 1350, 1180 cm-1.
N-Benzyl-3,4-diphenylpyrrolidine (6b) via Ditosylate 8; Typical
Procedure
MS (EI): m/z = 327 (M+), 312.
Anal. calcd for C24H25N: C, 88.02; H, 7.69; N, 4.27; found: C,
88.22; H, 7.75; N, 4.32.
A mixture of the ditosylate 8 (2.63 g, 5 mmol) and benzylamine
(13.39 g, 125 mmol) in toluene (2 mL) was heated at 120 °C for 2
h. Excess benzylamine was distilled out in vacum and the mixture
was dissolved in CH2Cl2 and the organic phase was washed with
H2O (10 mL), brine (15 mL) and dried (MgSO4). The solvent was
evaporated and the crude product was purified by column chro-
matograhy on silica gel using hexane/EtOAc (98:2) as eluent; yield:
1.37 g (88%). Spectroscopic data were identical with the sample
prepared following the sequence shown in Scheme 1.
The compounds 6b and 6c were also prepared following the above
procedure for the reduction.
6b
The product was purified by column chromatography on silica gel
using hexane/EtOAc (98:2) as eluent; yield: 2.4 g (76%)
IR (neat): n = 3061, 1602 cm-1.
1H NMR: d = 2.9-3.5 (m, 6 H), 3.9 (s, 2 H), 7.2-7.4 (m, 15 H).
13C NMR: d = 53.8, 60.8, 63.1, 126.1, 127.6, 128.0, 129.0, 129.8,
139.8, 144.9.
The derivatives 6a,d,e were also prepared following the same pro-
cedure.
6a
Yield: 1.3 g (83%). Spectroscopic data of the sample were identical
6a prepared following the sequence shown in Scheme 1.
MS (EI): m/z = 313 (M+).
Anal. cald for C23H23N: C, 88.25; H, 7.40; N, 4.47; found: C, 88.32;
H, 7.45; N, 4.51.
6d
Yield: 1.26 g (95%).
IR (neat): n = 3375, 1602 cm-1.
1H NMR: d = 2.36 (br s, 1 H), 2.8-3.4 (m, 8 H), 3.7 (t, 3 H, J =
16 Hz), 7.1-7.3 (m, 10 H).
6c
The product was purified by column chromatography on silica gel
using hexane/EtOAc (98:2) as eluent; yield: 2.46 g (75%); mp 130-
131 °C.
13C NMR: d = 52.9, 58.1, 60.6, 62.5, 126.5, 127.5, 128.6, 143.2.
MS (EI): m/z = 267 (M+), 236.
IR (KBr): n = 3060, 1232, 1155 cm-1.
1H NMR: d = 3.6-3.9 (m, 9 H), 6.8-7.0 (m, 4 H), 7.2-7.4 (m, 10
H).
13C NMR: d = 51.6, 55.7, 58.8, 112.2, 114.9, 119.6, 121.3, 126.7,
127.7, 128.5, 139.0, 141.5, 150.1.
MS (EI): m/z = 329 (M+).
Anal. calcd for C18H21NO: C, 80.97; H, 7.92; N, 5.24; found: c,
81.00; H, 7.9; N, 5.30.
6e
Yield: 1.26 g (90%).
IR (neat): n = 3061, 1602, 1155, 1118 cm-1.
1H NMR: d = 2.8-3.1 (m, 4 H), 3.3 (m, 2 H), 3.45 (s, 3 H), 3.5 (m,
2 H), 3.6 (t, 2 H, J = 10 Hz), 7.1-7.3 (m, 10 H).
13C NMR: d = 52.7, 55.8, 58.9, 62.9, 71.4, 126.3, 127.5, 128.4,
143.1.
Anal. calcd for C23H23NO: C, 83.96; H, 6.98; N, 4.25; found: C,
84.0; H, 6.98; N, 4.28.
N-Substituted 3,4-Diphenylpyrrolidines (Scheme 2)
dl-2,3-Diphenylbutane-1,4-diol (dl-7)
NaBH4 (1.82 g, 48 mmol) in anhyd THF (100 mL) was taken in a
two-necked septum capped round bottom flask. To the slurry
was added slowly a solution of I2 (5.1g, 20 mmol) in anhyd THF
(60 mL) during 2.5 h through a pressure equalizing dropping funnel
at 0 °C followed by a solution of 4 (2.7 g, 10 mmol) in THF (60 mL)
through a cannula at 0 °C. The contents were further stirred for 12
h at r.t. and refluxed for 4 h. The contents were cooled to 0 °C and
the excess hydride was carefully destroyed with 3 N HCl (10 mL).
After the gas evolution had ceased, the mixture was extracted with
Et2O (2 × 20 mL). The combined organic extracts were washed
with aq NaOH solution, H2O, brine and dried (MgSO4). The solvent
was evaporated and the product was purified by chromatography on
Chiral N-2-Methoxyethyl-3,4-diphenylpyrrolidine (Scheme 3)
(2S, 3S)-(+)-2,3-Diphenylsuccinic Acid [(2S,3S)-4a]
dl-2,3-Diphenylsuccinic acid (4) was resolved using (S)-proline
following a slightly modified procedure.14 The racemic 4 (27 g,
100 mmol) and (S)-proline (11.5 g, 100 mmol) were dissolved in
MeOH (300 mL) in a 500 mL round-bottomed flask by gentle heat-
ing over a water bath. The flask was closed with a glass stopper and
allowed to stand at r.t during 6 h. The precipitated material was fil-
tered and dried. The filtrate was concentrated to dryness and decom-
posed with a mixture of Et2O (200 mL) and H2O (200 mL). The
Synthesis 2000, No. 5, 703–706 ISSN 0039-7881 © Thieme Stuttgart · New York

706
V. D. Rao, M. Periasamy
PAPER
organic layer was separated and aqueous layer was extracted with
Et2O (2 × 100 mL). The combined organic extract was washed with
brine solution, dried (MgSO4), filtered and evaporated to afford
(2R,3R)-(-)-2,3-diphenylsuccinic acid [(2R,3R)-4], 16.7 g (62%,
29% ee); [a]D27 -109.0 (c = 684, EtOH) (Lit.15,16 [a]D13 -368.9 (c =
2.33, EtOH). The precipitate was decomposed by stirring in a mix-
ture of Et2O (100 mL) and H2O (100 mL). The organic layer was
separated and the aqueous layer was extracted with Et2O (2 × 100
mL). The combined organic extracts after further workup as out-
tography on silica gel using hexane/EtOAc (90:10) as eluent; yield:
0.51 g (90%); [a]DH2O +125.9 (c = 0.394, CH2Cl2). Indentical spec-
tral data (IR, 1H NMR and 13C NMR) were obtained as previously
described for dl-6e.
Acknowledgement
We are grateful to the CSIR, New Delhi for financial support. We
also thank the UGC for support under Special Assistance Program.
27
lined above gave (2S,3S)-(+)- 4; yield: 7.56 g (28%, 68% ee); [a]D
+254.0 (c = 0.448, EtOH), {Lit.15,16 [a]D15 +369.5 (c = 1.49, EtOH}.
References
The partially resolved (2S,3S)-(+)-4 (68% ee, 7.5 g, 27.77 mmol)
and (S)-proline (3.19 g, 27.27 mmol) were dissolved in MeOH
(82 mL) and kept for crystallization for 5 h. The precipitated mate-
rial was filtered. Workup of the precipitate as described above, gave
(1) Tomioka, K.; Nakajima, M.; Koga, K. J. Am. Chem. Soc.
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(4) Nakajima, M.; Tomioka, K.; Iitaka, Y.; Koga, K. Tetrahedron
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(5) Tomioka, K.; Nakajima, M.;;Koga, K. Chem. Lett. 1987, 65.
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(11) Bhanu Prasad, A. S.; Kanth, J. V. B.; Periasamy, M.
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27
(2S,3S)-(+)-4; yield: 4.8 g (64%, 96% ee); [a]D +354.0 (c = 1.0,
EtOH); mp 183-185 °C (Lit.15,16 mp 183 °C). After workup of the
filtrate, partially resolved (2S,3S)-(+)-4 was obtained; yield: 2.4 g
(32%, 43% ee); [a]D27 +160.0 (c = 0.508, EtOH).
(2S,3S)-(+)-2,3-Diphenylbutane-1,4-diol [(2S,3S)-7a]
This compound was prepared using NaBH4/I2 for the reduction as
27
outlined above for 7; yield: 2.1 g (86%); [a]D +47 (c = 0.25,
CHCl3) {Lit.17 [a]D21 +48.2 (c = 0.2490, CHCl3}; mp 101 °C.
IR (KBr): n = 3290, 3060, 1601 cm-1.
1H NMR: d = 2.2 (br s, 2 H), 3.25 (m, 2 H), 4.0 (m, 4 H), 6.9-7.0 (m,
4 H), 7.0-7.2 (m, 6 H).
13C NMR: d = 51.0, 65.5, 126.5, 128.1, 128.6, 140.6.
(2S,3S)-(+)-2,3-Diphenylbutane-1,4-ditosylate [(2S,3S)-8a]
This compound was prepared from the diol 7a (1.21 g, 5 mmol),
p-TsCl (3.8 g, 20 mmol), and anhyd pyridine (7.5 mL, 95 mmol)
following the procedure described above for 8; yield: 2.2 g (84%);
mp 108-109 °C; [a]D27 +8.0 (c = 0.41, benzene) (Lit.17 [a]D 23 +8.1
(c = 0.234, benzene).
IR (KBr): n = 1350 1180 cm-1.
Chiral N-2-Methoxyethyl-3,4-diphenylpyrrolidine [(2S,3S)-(+)-
6e]
(a) Wren, H.; Still, C. J. J. Chem. Soc. 1915, 107, 444.
(b) Wren, H.; Still, C. J. J. Chem. Soc.1915, 107, 1449.
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(17) Berova, N. D.; Kurtev, B. J. Tetrahedron 1969, 25, 2301.
A mixture of (2S,3S)-(+)-8a (1.052 g, 2 mmol) and 2-methoxyethyl-
amine (4.296 g, 50 mmol) in toluene (0.5 mL) was heated at 120 °C
for 2 h. Excess 2-methoxyethylamine was distilled out and the mix-
ture was dissolved in CH2Cl2. The organic phase was washed with
H2O (5 mL), brine (10 mL) and dried (MgSO4). The solvent was
evaporated and the crude product was purified by column chroma-
Article Identifier:
1437-210X,E;2000,0,05,0703,0706,ftx,en;Z09399SS.pdf
Synthesis 2000, No. 5, 703–706 ISSN 0039-7881 © Thieme Stuttgart · New York