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Synlett 2002(7): 1105-1106
DOI: 10.1055/s-2002-32597
LETTER
© Georg Thieme Verlag Stuttgart · New York

Convenient Synthesis of 3-(S)-Amino-γ-butyrolactone

Martha Sibrian-Vazquez, David A. Spivak*
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Fax: +1(225)5783458; e-Mail: David_Spivak@chem.lsu.edu;
Further Information

Publication History

Received 15 April 2002
Publication Date:
07 February 2007 (online)

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Abstract

An efficient two step conversion of N-t-Boc-l-aspartic acid β-benzyl ester to enantiopure 3-(S)-amino-γ-butyrolactone is described. In this route, chemoselective reduction of the α-carboxylic group in the starting material via a mixed anhydride with NaBH4 afforded the corresponding alcohol in 95% yield without any loss of the optical purity. Subsequent acidic hydrolysis of the N-protected β-amino alcohol not only deprotected the amino group, but also produced the desired γ-lactone in 98% yield with complete retention of the optical activity.

Key words

amino acids - amino alcohols - lactones - reductions - ring closure

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12

Benzyl (3 S )-[( tert -butoxycarbonyl)amino]-4-hydroxy-butanoate(3). Prepared from N-t-boc-l-aspartic acid
β-benzyl ester following a literature procedure [13d] as a white solid. Yield 95%, ee > 98%. Enantiomeric excess was determined by HPLC using a normal phase Chiralpak AD column, hexanes-isopropanol 90:10, 1 mL/min, at 250 nm, mp 62-63.8 °C [α]D 25 -6.0 (c = 1, MeOH); lit. [13e] [α]D -6.0 (c = 1, MeOH). 1H NMR (250 MHz; CDCl3), δ: 7.33 (s, 5 H), 5.28 (s, 1 H), 5.11 (s, 2 H), 4.00 (s, 1 H), 3.64 (d, J = 4.7 Hz, 2 H), 2.88 (s, 1 H), 2.64 (d, J = 6.2 Hz, 2 H), 1.42 (s, 9 H). 13C NMR (67.5 MHz; CDCl3) δ: 172.06, 156.23, 135.99, 129.02, 128.76, 128.66, 107.82, 80.29, 67.05, 49.87, 36.47, 28.76. MS (FAB) (M + H+) calcd 310.16, found 310.10. Anal. Calcd. for C16H23NO5: C, 62.12; H, 7.49; N, 4.53. Found C, 61.72; H, 7.39; N, 4.41.

14

3-( S )-amino-γ-butyrolactone hydrochloride(1) The amino alcohol 4 (1.26g, 4 mmol) was treated with 40 mL of 2 M HCl in diethyl ether. The temperature was kept at 0 °C for 6 h, then allowed to rise to room temperature, and stirred for 18 hours. The excess of HCl and ether were evaporated first under a stream of N2 and then under vacuum. The residue, a white solid was filtered out, washed with ethyl ether (3 × 20 mL), and dried at room temperature. Yield 98%. mp 182-184 °C. [α]D 25 -59.3 (c = 1, H2O); lit. [11] [α]D 20 + 56.7 (c = 1, H2O) (R) form. 1H NMR [250 MHz; (DMSO-d6)] δ: 8.76 (s, 3 H), 4.5 (dd, J = 10.4 Hz, J = 6.6 Hz, 1 H), 4.36 (dd, J = 10.4 Hz, J = 2.7 Hz, 1 H), 4.10 (m, 1 H), 3.0 (dd, J = 18.3, J = 8.5 Hz, 1 H), 2.57 (dd, J = 18.3 Hz, J = 2.9 Hz, 1 H). 13C NMR: [67.5 MHz; (DMSO-d6)] δ: 175.39, 71.05, 41.19, 33.42. MS (FAB) (M + H+) calcd. 102.1, found 102.1. Anal. Calcd. for C4H8ClNO2: C, 34.92; H, 5.86; N, 10.18; Cl, 25.77. Found C, 34.99; H, 5.62; N, 10.08; Cl, 25.12.