| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1345086 | Tetrahedron: Asymmetry | 2014 | 4 Pages |
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)
