A Continuous-Flow Approach to 3,3,3-Trifluoromethylpropenes: Bringing Together Grignard Addition, Peterson Elimination, Inline Extraction, and Solvent Switching

被引：31

作者：

Hamlin, Trevor A. ^{[1
]}

Lazarus, Gillian M. L. ^{[1
]}

Kelly, Christopher B. ^{[1
]}

Leadbeater, Nicholas E. ^{[1
,2
]}

机构：

[1] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA

[2] Univ Connecticut, Ctr Hlth, Dept Community Med & Hlth Care, Farmington, CT 06030 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2014年 / 18卷 / 10期

基金：

美国国家科学基金会;

关键词：

TRIFLUOROMETHYL KETONES; MEDICINAL CHEMISTRY; DIPEPTIDE ISOSTERES; EFFICIENT SYNTHESIS; PEPTIDE ISOSTERES; FLUORINE; OLEFINATION; REACTOR; SEPARATION; REAGENTS;

D O I：

10.1021/op500190j

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A continuous-flow approach to the synthesis of 3,3,3-trifluoromethylpropenes involving Grignard addition of, (trimethylsilyl)methylmagnesium chloride to a trifluoromethyl ketone followed by dehydrative desilylation of the alpha-trifluoromethyl-beta-hydroxysilyl alcohol using trimethylsilyl trifluoromethanesulfonate is reported. An inline aqueous/organic extraction and a concomitant solvent switch were key to the success of the methodology. Transition from batch to continuous flow conditions allows for higher yields, shorter reaction times, and facile scale out.

引用

收藏

页码：1253 / 1258

页数：6

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