17-Ethynylestradiol 3-methyl ether

Ethynylestradiol 3-methyl ether, 4, 20 17-Ethynyl-19-nortestosterone, 8, 44, 52 16/3-(Ethylthio)estradiol 3-methyl ether, 5 Experimental conditions for Birch reduction, 25... 

A small portion of 14-1 that fails to react on kilogram-scale Birch reduction will tag along the next set of transformations oxidation and subsequent ethynylation. This leads to contamination of the final product by the potent estrogen 17-ethynylestradiol 3-methyl ether (15-2). This very small impurity in the final product is now known to be essential for contraceptive efficacy. A carefully measured small amount of an estrogen is now included in virtually all oral contraceptives. 

Fragmentation reactions. Silver carbonate on Celite (Fetizon s reagent) quantitatively cleaves steroidal 17-elhynyl alcohols. Thus treatment of 17x-ethynylestradiol methyl ether (1) with silver carbonate on Celite in toluene under reflux gives estrone methyl ether (2) in quantitative yield. In the same way, dehydroepiandrosterone (4) was obtained from (3). 

Reaction of estrone with a metal acetylide affords 17a-ethynyl-173-hydroxy-estradiol (etbynylestradiol, 30a EE). This compound is equipotent with estradiol by subcutaneous administration, but it is 15 to 20 times as active when administered orally. Ethynylation of the methyl ether of estradiol analogously affords mestranol (30b), It should be noted that the same factors apply in these reactions as in previously discussed reductions at 17 almost the sole products of these reactions are those which result from attack of reagent from the least hindered a side of the steroid. Ethynylestradiol and mestranol are of special commercial significance since the majority of the oral contraceptives now on sale incorporate one or the other of the compounds as the estrogenic component. 

Chemical Name 3-methoxy-19-nor-17a-pregna-1,3,5( 10)-trien-20-yn-17-ol Common Name 17a-ethynylestradiol 3-methyl ether Structural Formula ... 

Absorption of orally administered, relatively lipophilic compounds, such as estrone or estradiol, occurs mainly in the intestine. The bacteria that colonize the gut are, however, particularly adept at converting those compounds by attack at the 17 position to very water-soluble derivatives that defy absorption. Alkylation of that position avoids this catabolic pathway and consequently enhances bioavailability on oral administration. The reaction of 17-keto steroids with nucleophiles illustrates the high degree of stereospecifity that is maintained in many steroid reactions approach of that carbonyl group from the (3 face is virtually forbidden by the presence of the adjacent 18 methyl. The reaction products consequently consist of almost pure isomers from attack at the a face. Reaction of estradiol with lithium acetylide thus gives ethynylestradiol (9-2) [9] the corresponding alkylation of estradiol 3-methyl ether (9-1) leads to mestranol (9-3) [10]. Both compounds are potent orally active... 

ETHYNYLENEBIS(CARBONYLOXY)BIS(TRIPHENYL STANNANE) see BLS900 ETHYNYLESTRADIOL see EEH500 17-a-ETHYNYLESTRADIOL see EEH500 17-a-ETHYNYLESTR DIOL-17-P see EEH500 ETHYNYLESTRADIOL-3-METHYL ETHER see MKB750... 

C21H1803 benzyl 4-benzyloxybenzoate 56442-22-9 25.00 1.1802 2 32876 C21H2602 ethynylestradiol 3-methyl ether 72-33-3 25.00 1.0341 2... 

Names synonyms ESTRONE BENZOATE ETHYNYL ESTRADIOL 17 ethinyl estradiol 17 -ethynyl 1.3,5 estratriene-3.17 >diot. MESTRANOL ethynylestradiol 3>methyl ether 3 methoxy l7 -ethynyl-l.3.5(10>-estrairiene 17 ol 17a-ethynyl tradiol-3-meihyl ether 3>methoxy> 19 nor-17a pregna> 1.3,5.(rien-20-yn- 7-ol. 

Cleavage. 17a-Ethynylestradiol 3-methyl ether refluxed with Ag-carbonate-on-Celite in toluene -> product. Y ca. 100%. F. e. s. G. R. Lenz, Chem. Commun. 1972,468. 

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