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Synlett 2016; 27(02): 309-312
DOI: 10.1055/s-0035-1560489
DOI: 10.1055/s-0035-1560489
letter
An Improved Synthesis of β-Cyano-l-Alanine Esters and Amides
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
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560489.
- Supporting Information
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References and Notes
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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 1a–c (0.10 mmol) and alcohol or amine 2a–n (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.