New highly stereoselective synthesis of (Z)-4-hydroxytamoxifen and (Z)-4-hydroxytoremifene via McMurry reaction

Journal of Organic Chemistry

Volumn 61, Issue 11, 1996, Pages 3890-3893

  Gauthier, Sylvain ^a   Mailhot, Josée ^a   Labrie, Fernand ^a  

^a LAVAL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXYTAMOXIFEN; 4 HYDROXYTOREMIFENE;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER;

EID: 0029893855     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo952279l     Document Type: Article

References (26)

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20. We believe that carbometalation of alkynylsilanes cannot be a successful method for the preparation of compound 4.
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22. (a) We recovered 45% of starting material and 8% of corresponding dialkylated compound 16.
23. (b) We recovered 30% of starting material and 25% of corresponding dipivaloate compound 17.
24. b). Moreover, Z isomers 3 and 4 have upfield NMR signals of the 2-dimethylaminoethoxy chain protons compared to the corresponding E isomers 5 and 6 (see ref. 7c, 7d and 10a). (Formula Presented)
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26. When the benzoate as a protecting group was used in the synthesis, we obtained low yield (20-30%) and decreased E/Z ratio (19:1 in the best cases) of desired amine. This phenomena could be explained via the transesterification. In order to decrease the amount of diester olefin and other byproducts, the less reactive pivaloate as a protecting group was used. (17)2-(Dimethylamino)ethyl chloride was obtained by treating 2-(dimethylamino)ethyl chloride hydrochloride with saturated sodium carbonate for 30 min. Then, the amine was extracted with ether, and the solution was dried and distilled under atmospheric pressure (bp 95-100°C, 80% yield).