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W.-Q. Lin et al. / Tetrahedron: Asymmetry 12 (2001) 1583–1587
4.6. Ethyl (R)-2-hydroxyl-4-phenylbutanoate (R)-1
Acknowledgements
Potassium propionate (7.0 g, 0.063 mol) was added to a
solution of 7 (6.0 g, 0.021 mol) in ethanol (200 mL).
The resulting mixture was stirred under reflux for 48 h,
then cooled to room temperature and filtered. The
filtrate was evaporated under reduced pressure. The
residue was dissolved in ethyl acetate (200 mL). The
resulting solution was washed twice with brine and
dried over anhydrous sodium sulfate. The solvent was
removed in vacuo to give 8, which was directly used for
the next hydrolysis without purification.
We are extremely grateful to the National Natural
Science Foundation of China for supporting this
research (No 29790124).
References
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To the solution of 8 in ethanol (400 mL) was added
potassium carbonate (9 g, 0.064 mol). The resulting
mixture was stirred at room temperature overnight and
filtered. The filtrate was neutralized with aqueous HCl
(6 M) and evaporated under reduced pressure. The
residue was partitioned between ethyl acetate (150 mL)
and water (50 mL). The organic layer was washed with
brine, and dried (anhydrous Na2SO4). The solvent was
evaporated to give (R)-1 as an oil (3.6 g, 83% from 7)
e.e.=97% (GC Varian 3380, CP-Chirasil-Dex, Tc=
140°C).
4.7. Ethyl (R)-2-azido-4-phenylbutanoate (R)-9
A solution of 7 (1.8 g, 6.3 mmol) in DMF (10 mL) was
treated with sodium azide (0.5 g, 7.7 mmol) at room
temperature for 6 h. To the reaction mixture, ethyl
acetate (80 mL) and water (40 mL) were added. The
organic phase was separated and dried over anhydrous
Na2SO4. The solvent was evaporated to give 9 as a pale
yellow oil (1.37 g, 87%) e.e.=97% (HPLC, OB column,
5% iso-propanol–hexane, 1.0 mL/min, UV 220 nm). IR
(neat) cm−1: 2105 (NꢀNꢀN), 1738 (CꢀO); 1H NMR (300
MHz, CDCl3): l (ppm) 1.32–1.37 (3H, t, J=7.1 Hz,
4. (a) Huerta, F. F.; Santosh Laxmi, Y. R.; Ba¨ckvall, J.-E.
Org. Lett. 2000, 2, 1037; (b) Chadha, A.; Manohar, M.
Tetrahedron: Asymmetry 1995, 6, 651; (c) Baldaro, E.;
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OCH2CH
(2H, m, ArCH
N3CHCO), 4.26 (2H, q, J=7.1 Hz, OCH
7.37 (5H, m, Ar-H
6
3), 2.10–2.21 (2H, m, ArCH2CH
6
2), 2.75–2.84
2), 3.85 (1H, dd, J=5.08, 8.72 Hz,
6
6
6 2CH3), 7.24–
6
); 13C NMR (75 MHz, CDCl3): l
(ppm) 14.1, 31.7, 32.9, 61.1, 61.8, 126.3, 128.5, 140.1,
170.4.
6. Chadha, A.; Manohar, M.; Soundararajan, T.;
Lokeswari, T. S. Tetrahedron: Asymmetry 1996, 7, 1571.
7.
D-Homophenylalanine ethyl ester hydrochloride (2) has
4.8.
D
-Homophenylalanine ethyl ester hydrochloride 2
been prepared via asymmetric synthesis and enzymatic
methods, see: (a) Li, X.; Yeung, C.; Chan, A. S. C.; Lee,
D.; Yang, T. Tetrahedron: Asymmetry 1999, 10, 3863; (b)
Andres, C.; Maestro, A.; Pedrosa, R.; Perez-Encabo, A.;
Vicente, M. Synlett 1992, 45; (c) Chen, S. T.; Wang, K.
T. J. Chin. Chem. Soc. (Taipei ) 1999, 46, 301; (d) Houng,
J. Y.; Wu, M. L.; Chen, S. T. Chirality 1996, 8, 418.
To a stirred solution of 9 (1.3 g, 5.2 mmol) in ethanol
(15 mL) and water (5 mL), ammonium chloride (0.6 g,
11 mmol) and zinc powder (0.4 g, 11 mmol) were
added. The reaction mixture was stirred under reflux
for 10 min and cooled to room temperature, filtered
and evaporated. The residue was dissolved in a mixture
of ethyl acetate (100 mL) and 10% aqueous ammonia
(30 mL). The organic layer was dried (anhydrous
Na2SO4) and filtered. Anhydrous hydrogen chloride
was bubbled into the filtrate. The solution was evapo-
rated to give a white solid, which was recrystallized
from ethanol and ether to afford 2 as a white crystalline
solid (1.17 g, 87%). [h]2D5=−38.6 (c 1 H2O), e.e.: 99%
(HPLC, CR column, HClO4 (aq., pH 2), 0.8 mL/min,
T=18°C, UV 215 nm).
8. The Friedel–Crafts reaction of a-acetyloxybutanedioic
anhydride 4 with 1,2-dichlorobenzene has been reported,
see: Giordani, A.; Pevarello, P.; Cini, M.; Bormetti, R.;
Greco, F.; Toma, S.; Speciale, C.; Varasi, M. Bioorg.
Med. Chem. Lett. 1998, 8, 2907.
9. Henrot, S.; Larcheveˆque, M.; Petit, Y. Synth. Commun.
1986, 16, 183.
10. Compound 5 has been prepared by enzymatic reduction
of a,g-dioxobenzenebutanoic acid, see: Casy, G. Tetra-
hedron Lett. 1992, 33, 8159.