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Synthesis 2012(6): 875-880  
DOI: 10.1055/s-0031-1289724
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Multikilogram-Scale Synthesis of (R)-Methyl 2-[(1r,4R)-4-(tert-Butoxy­carbonylamino)cyclohexyl]-2-(2-nitrophenylsulfonamido)acetate - A Doubly Protected Building Block with Three Points of Variation

Gregory Carr*a, Sam Butterwortha, Phil Walkera, Folkert Reckb, Bolin Gengb, Lakshmipathi Pandarinathanb
a Astrazeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
b Infection Innovative Medicines Unit, AstraZeneca R & D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA
Fax: +44(1625)513910; e-Mail: greg.carr@astrazeneca.com;
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Publication History

Received 19 October 2011
Publication Date:
27 February 2012 (online)

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Abstract

A robust and scalable synthesis of (R)-methyl 2-[(1r,4R)-4-(tert-butoxycarbonylamino)cyclohexyl]-2-(2-nitrophenylsulfon­amido)acetate is reported. This serves as a scaffold for the preparation of trans-substituted aminocyclohexanes. The key synthetic step is the reduction of d-4-hydroxyphenylglycine, or a protected equivalent, to achieve the required regiochemistry across the cyclohexyl ring.

Key words

chirality - diastereoselectivity - hydrogenation - protecting groups - reduction

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