(3S)-4- 溴-3- 羟基丁酸乙酯经缩合、不对称生物催化还原及羟基保护制得[(4R,6S)-6- 溴甲基-2,2- 二甲基-1,3- 二氧杂环己烷-4- 基] 乙酸叔丁酯( 5)，5 在溴化亚铜及含氮化合物配体作用下与硝基甲烷缩合后，经雷尼镍催化氢化还原制得阿托伐他汀钙中间体[(4R,6R)-6-(2- 氨基乙基)-2,2- 二甲基-1,3- 二氧杂环己烷-4- 基] 乙酸叔丁酯，总收率约41％。
Abstract
tert-Butyl [(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate, the intermediate of atorvastatin calcium, was synthesized from (3S)-ethyl-4-bromo-3-hydroxybutanoat by condensation, asymmetric biocatalytic reduction and hydroxyl protection to give tert-butyl [(4R,6S)-6-bromomethyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate, which was subjected to condensation with CH3NO2 in the presence of CuBr/ligand, followed by reduction with an overall yield of about 41％.
关键词
[(4R /
6R)-6-(2-氨基乙基)-2 /
2-二甲基-1 /
3-二氧杂环己烷-4-基]乙酸叔丁酯 /
阿托伐他汀钙 /
降血脂药 /
中间体 /
合成
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Key words
tert-butyl [(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate /
atorvastatin calcium /
hypolipidemic drug /
intermediate /
synthesis
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参考文献
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脚注
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