کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1345086 1500345 2014 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
An improved process for chiron synthesis of the atorvastatin side chain
ترجمه فارسی عنوان
یک فرآیند بهبود یافته برای سنتز چیرون زنجیره جانبی اتورواستاتین
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
چکیده انگلیسی

An improved and practical synthesis of tert-butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetate 3 has been developed for supplying this key chiral side-chain of atorvastatin by using a Blaise reaction of (S)-4-chloro-3-((trimethylsilyl)oxy)butanenitrile 7 and the Raney Ni catalyzed hydrogenation of tert-butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate 12 as the key steps. This nine-step route from (R)-epichlorohydrin afforded the target compound in 55% overall yield of high chemical and enantiomeric purity.

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(R)-3-((Trimethylsilyl)oxy)hex-5-enenitrileC9H17NOSi[α]D21 = −2.2 (c 1.0, MeOH).Source of chirality: (R)-epichlorohydrinAbsolute configuration: (3R)

(R)-tert-Butyl 5-hydroxy-3-oxooct-7-enoateC12H20O4[α]D21 = −10.3 (c 1.0, MeOH)Source of chirality: (R)-epichlorohydrinAbsolute configuration: (5R)

(3R,5R)-tert-Butyl 3,5-dihydroxyoct-7-enoateC12H22O4[α]D21 = −10.5 (c 1.0, MeOH)Source of chirality: (R)-epichlorohydrin; Stereoselective reductionAbsolute configuration: (3R,5R)

tert-Butyl 2-((4R,6R)-6-allyl-2,2-dimethyl-1,3-dioxan-4-yl)acetateC15H26O4dr = 99:1[α]D21 = +0.7 (c 1.0, MeOH)Source of chirality: (R)-epichlorohydrin; Stereoselective reductionAbsolute configuration: (4R,6R)

tert-Butyl 2-((4R,6R)-6-(-2-oximeethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetateC14H25NO5[α]D24 = −0.6 (c 1.0, MeOH)Source of chirality: (R)-epichlorohydrin; Stereoselective reductionAbsolute configuration: (4R,6R)

tert-Butyl ((4R,6R)-6-aminoethyl-2,2-dimethyl-1,3-dioxan-4-yl)acetateC14H27NO4[α]D14 = +16.9 (c 0.34, CHCl3)Source of chirality: (R)-epichlorohydrin; Stereoselective reductionAbsolute configuration: (4R,6R)

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Tetrahedron: Asymmetry - Volume 25, Issues 16–17, 15 September 2014, Pages 1205–1208
نویسندگان
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