Regioselective C2-lithiation of N-Boc-3-bromopyrroles: a novel approach towards the synthesis and scale-up of 3-(2-formyl-4-methyl-1-H-pyrrol-3-yl)propanoic acid

被引：1

作者：

Dai, Donghua ^{[1
]}

Venepalli, Bhaskar Rao ^{[1
]}

机构：

[1] CiventiChem, Cary, NC 27519 USA

来源：

TETRAHEDRON LETTERS | 2015年 / 56卷 / 19期

关键词：

Regioselective lithiation; N-Boc-3-bromopyrrole; 3-(2-Formyl-4-methyl-1-H-pyrrol-3-yl)propanoic acid; SU5402; Negishi coupling; DIRECTED ORTHO-METALATION; CROSS-COUPLING REACTION; PYRROLES; RECEPTOR; LITHIATION; INHIBITORS; REAGENTS; COMPLEX;

D O I：

10.1016/j.tetlet.2015.03.035

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

ortho-Lithiation of N-Boc-3-bromopyrroles (7b, 7d) with LDA in THF at 75 degrees C, followed by reactions with ethyl formate gave exclusive C2-formylpyrroles (9b, 9c, 9d, 9e) in good yields. This methodology was applied to the synthesis of 3-(2-formyl-4-methyl-1-H-pyrrol-3-yl)propanoic acid (4a), a penultimate precursor to SU5402. The process for making 4a has also been optimized which involves a nonchromatography eight-step synthesis with an overall 18% yield. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：2402 / 2405

页数：4

共 36 条

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