Estrone methyl ether 17-ethylene ketal

The third route for the synthesis of estrone methyl ether (133) passes through the ethylene ketal (393), the synthesis of which has been described in Scheme 38. Selective hydrogenation of the ketal (393) leads to the trans-C/D ketal (401), which can also be obtained in two stages by the hydrogenation and ketalization of the ketone (395). The reduction of the A -bond with lithium in liquid ammonia and hydrolysis of the ketal grouping gives the desired product (133) [489, 511]. 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

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