Synlett 2016; 27(02): 309-312
DOI: 10.1055/s-0035-1560489
letter
© Georg Thieme Verlag Stuttgart · New York

An Improved Synthesis of β-Cyano-l-Alanine Esters and Amides

Guoxin Wang*
a   Key Laboratory of Structural Biology and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. of China   Email: wanggx@pkusz.edu.cn   Email: lizg@pkusz.edu.cn
,
Longjian Chen
a   Key Laboratory of Structural Biology and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. of China   Email: wanggx@pkusz.edu.cn   Email: lizg@pkusz.edu.cn
,
Xiaodan Cai
a   Key Laboratory of Structural Biology and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. of China   Email: wanggx@pkusz.edu.cn   Email: lizg@pkusz.edu.cn
,
Zigang Li*
a   Key Laboratory of Structural Biology and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. of China   Email: wanggx@pkusz.edu.cn   Email: lizg@pkusz.edu.cn
,
Ming Luo
a   Key Laboratory of Structural Biology and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, P. R. of China   Email: wanggx@pkusz.edu.cn   Email: lizg@pkusz.edu.cn
b   Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA   Email: mluo@gsu.edu
› Author Affiliations
Further Information

Publication History

Received: 31 July 2015

Accepted after revision: 13 September 2015

Publication Date:
30 September 2015 (online)


Abstract

We have developed a novel, mild, efficient, and scalable protocol for the synthesis of N-protected β-cyano-l-alanine esters or ­amides from N-protected l-asparagin. This protocol avoided the use of toxic or unpleasant reagents and was easy to operate in laboratory.

Supporting Information

 
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  • 10 General Procedures for the Synthesis of β-Cyano-l-Alanine Esters and Amides To a stirred solution of N-protected l-asparagin 1ac (0.10 mmol) and alcohol or amine 2an (0.12 mmol) in CH2Cl2 (10 mL), EDC·HCl (0.30 mmol), and DMAP (0.02 mmol) were added at 0 °C. This reaction mixture was stirred for 12 h at r.t. Then the reaction mixture was poured in H2O (10 mL) and extracted with CH2Cl2 (20 mL). The organic phase was separated, dried, and subjected to flash column chromatography (EtOAc–hexane, 1: 4) to afford the desired compounds as white solids.
  • 11 Selected Spectral Data for Compound Benzyl 2-[(tert-Butoxycarbonyl)amino]-3-cyanopropanoate (4a) Yield: 288 mg (95%); white crystals, mp 131–133 °C. 1H NMR (300 MHz, CDCl3): δ = 7.45–7.35 (m, 5 H, ArH), 5.55 (d, J = 6.6 Hz, 1 H, NH), 5.26 (s, 2 H, CH2), 4.55–4.51 (m, 1 H, COCH), 3.00–2.89 (m, 2 H, CH2CN), 1.47 [s, 9 H, OC(CH3)3]. 13C NMR (75 MHz, CDCl3): δ = 169.13, 155.05, 134.74, 116.54, 81.06, 68.40, 50.53, 28.36, 21.78. ESI-HRMS: m/z [M + Na]+ calcd for C16H20N2O4 + Na: 327.1321; found: 327.1309.