Mono-Chlorination of Electron-Rich Arylalkyl- and Heteroarylalkyl-amines and Amino Acids Using Sulfuryl Chloride

Guixue Yu; Helen J. Mason; Kim Galdi; Ximao Wu; Lyndon Cornelius; Ning Zhao; Michael Witkus; William R. Ewing; John E. Macor

doi:10.1055/s-2003-37362

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Synthesis 2003(3): 0403-0407
DOI: 10.1055/s-2003-37362

PAPER

Mono-Chlorination of Electron-Rich Arylalkyl- and Heteroarylalkyl-amines and Amino Acids Using Sulfuryl Chloride

Guixue Yu*^a, Helen J. Mason^a, Kim Galdi^a, Ximao Wu^a, Lyndon Cornelius^a, Ning Zhao^b, Michael Witkus^b, William R. Ewing^a, John E. Macor^a
^a Discovery Chemistry, Bristol-Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA
Fax: +1(609)8183450; e-Mail: guixue.yu@bms.com;
^b Preclinical Candidate Optimization, Bristol-Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA

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Publication History

Received 11 October 2002
Publication Date:
19 February 2003 (online)

Abstract
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Abstract

Sulfuryl chloride has been used to mono-chlorinate electron-rich arylalkyl- and heteroarylalkyl-amines and amino acids in a mild and efficient one-pot transformation with straightforward purification. Protection of the amines was not needed, and racemization of the chiral amino acids was minimal.

Key words

halogenation - chlorination - sulfuryl chloride - amino acids - amines

References

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8

Chiral purity (ee%) was determined by chiral HPLC. Specific conditions were: 9 and 10 used Chiralcel OD-H with heptane-i-PrOH-Et₂NH (95:5:0.1) at a flow rate of 0.8 mL/min; 11 and 12 used Chiralpak AD with heptane-i-PrOH-Et₂NH (98:2:0.1) at a flow rate of 1.0 mL/min, 13 and 14 used Chiralpak OJ with heptane-MeOH-EtOH-Et₂NH (85:7.5:7.5:0.1) at a flow rate of 1.0 mL/min; 15 and 16 used Chiralpak AD with heptane-i-PrOH-Et₂NH (95:5:0.1 v/v/v) at a flow rate of 1.0 mL/min.