4032
M. Lasa et al. / Tetrahedron: Asymmetry 16 (2005) 4022–4033
4) = 0.7. IR (neat) 3416.3, 3355.6, 1728.9 (b),
1489.8 cmꢀ1 1H NMR (CDCl3, 400 MHz, 55 ꢁC) d
4.17.2. (1S,2S)-N-Z-c4Phe-OH (1S,2S)-20. In a similar
way to that described above, starting from (1S,2S)-19
(247 mg, 0.7 mmol), (1S,2S)-20 was obtained as an oil
(194 mg, 0.6 mmol, 85% yield). [a]D = +40.1 (c 0.86,
CHCl3). Spectroscopic data are the same as those
described for rac-20.
.
1.16 (t, 3H, J = 6.7 Hz), 2.12–2.20 (m, 1H), 2.36–2.46
(m, 1H), 2.84 (td, 1H, J = 9.3, J = 12.6 Hz), 3.92 (t,
1H, J = 9.0 Hz), 4.14 (br s, 1H), 4.64 (m, 1H), 4.94 (d,
1H, J = 12.3 Hz), 4.89 (d, 1H, J = 12.3 Hz), 7.08–7.27
(m, 10H). 13C NMR (CDCl3, 100 MHz, 55 ꢁC) d 14.10,
20.60, 27.38, 46.51, 61.34, 62.08, 66.69, 127.60, 127.99,
128.05, 128.37, 128.83, 136.40, 136.50, 155.57, 172.71.
4.18. Synthesis of cis-c4Phe hydrochloride rac-5
A solution of cis-Z-c4Phe-OH rac-20 (228 mg, 0.7 mmol)
in ethanol (7 mL) was treated at room temperature with
10% palladium–carbon (50 mg) in a hydrogen atmo-
sphere. The reaction was carefully controlled by TLC
monitoring (eluent: CH2Cl2/EtOAc 8/2) to avoid prod-
uct decomposition. The catalyst was filtered off and the
solvent was evaporated. The resulting residue was trea-
ted with a solution of ethyl acetate saturated with HCl
for 30 min. The solvent was evaporated and the solid
was redissolved in water and washed with several addi-
tional portions of CH2Cl2 and then lyophilized to give
rac-5 (135 mg, 0.6 mmol, 85% yield). Mp 158–161 ꢁC
4.16. Resolution of rac-19: (1R,2R)-19 and (1S,2S)-19
HPLC resolution of a solution of cis-racemate rac-19
(710 mg) in CHCl3 (2.4 mL) was carried out by succes-
sive injections of 0.2 mL on a 150 · 20 mm ID column
filled with mixed 10-undecenoate/3,5-dimethylphenyl-
carbamate of cellulose bonded on allylsilica gel and
using a mixture of n-hexane/2-propanol/acetone 94/4/2
as the eluent (flow rate: 14 mL/min). A total of 13 injec-
tions was required, with one injection performed every
10 min. Four separate fractions were collected. The first,
second, third and fourth fractions contained, respec-
tively, 100/0 (320 mg), 65/35 (35 mg), 0.5/99.5
(100 mg) and 0.1/99.9 (235 mg) mixtures of the first
and the last eluted enantiomers. Spectroscopic data for
both enantiomers are the same as those described for
rac-19:
(dec). IR (nujol) 3300–2400, 1736.6, 1569.8 cmꢀ1 1H
.
NMR (D2O, 300 MHz) d 2.12–2.18 (m, 1H), 2.38–2.46
(m, 1H), 2.68–2.78 (m, 1H), 2.83 (td, 1H, J = 9.2,
12.6 Hz), 4.36 (t, 1H, J = 9.5 Hz), 7.29–7.50 (m, 5H).
13C NMR (D2O, 75 MHz) d 18.94, 26.16, 44.77, 62.96,
127.76, 128.26, 129.19, 135.04, 173.25.
(1R,2R)-19: [a]D = ꢀ20.9 (c 0.97, CHCl3),
(1S,2S)-19: [a]D = +20.1 (c 1.00, CHCl3).
4.17. Synthesis of cis-Z-c4Phe-OH rac-20
Acknowledgements
´
Financial support from Ministerio de Educacion y Cien-
cia—FEDER (project CTQ2004-5358) and Diputacion
General de Aragon is gratefully acknowledged. M. Lasa
´
´
would like to thank CSIC for an FPU grant.
A solution of NaOH (100 mg, 2.5 mmol) in water was
added to a suspension of rac-19 (1.0 mmol, 353 mg) in
water (5 mL). The reaction mixture was heated under
reflux until complete consumption of the starting material
was achieved (TLC monitoring, eluent: hexane/EtOAc
8/2). The mixture was cooled to room temperature
and water (10 mL) was added. The aqueous layer was
washed with dichloromethane (15 mL), acidified with
hydrochloric acid to pH 2–3 and then extracted with
dichloromethane (3 · 15 mL). Concentration of the
organic layer resulted in the precipitation of rac-20 as
a white solid (299 mg, 0.9 mmol, 92%). Mp 128 ꢁC (hex-
ane). Rf (CH2Cl2/EtOAc 8/2) = 0.5. IR (nujol) 3334.3,
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cal procedure to that described above was applied to
transform (1R,2R)-19 (283 mg, 0.8 mmol) into
(1R,2R)-20, which was obtained as an oil (234 mg,
0.7 mmol, 90% yield). [a]D = ꢀ39.8 (c 0.73, CHCl3).
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