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Process for the synthesis of (11b, 17a) - 17 - acetoxy - 11 - 3 - methyl - 4 - oxo - norpregn eno
专利权人:
RICHTER GEDEON NYRT
发明人:
申请号:
ARP140104409
公开号:
AR098524A1
申请日:
2014.11.25
申请国别(地区):
AR
年份:
2016
代理人:
摘要:
Claim on formula compound (3),(4)(5)(6)(7)(8)Page: 1(9)and (9). Claim 1: A process for the synthesis of (11b, 17a) -17-acetoxy-11-methyl-19-norpregn-4-en-3,20-dione of formula (1) characterized in that 3,3 is reacted -ethylenedioxy-5a, 10a-epoxy-17a- (trimethylsilyloxy) -5a-estr-9 (11) -en-17b-carbonitrile of formula (2) with methylmagnesium chloride in the presence of copper (l) chloride in a solvent of the ether type at a temperature not higher than 15 ° C, the 3,3-ethylenedioxy-11b-methyl-5a-hydroxy-17a- (trimethylsilyloxy) -estr-9-en-17b-carbonitrile of formula (3) is reacted with trimethylsilyl chloride in the presence of a tertiary amine in an ether or halogen type solvent at a temperature not higher than 40ºC,3,3-ethylenedioxy-11b-methyl-5a, 17a-bis (trimethylsilyloxy) -estr-9-en-17b-carbonitrile of formula (4) obtained with an excess of diisobutylaluminum hydride in an ether type solvent is reduced. at a temperature not higher than 0 ° C, the 3,3-ethylenedioxy-11b-methyl-5a, 17a-bis (trimethylsilyloxy) -estr-9-en-17b-carbaldehyde of formula (5) is reacted without further purification with methylmagnesium chloride to obtain the 20-hydroxypregnan derivative, then the protecting groups are removed by adding KHSO₄ aqueous solution keeping the temperature below 30ºC,(11b, 17a, 20x) -11-methyl-norpregna-4,9-dien-17,20-diol obtained from formula (6) is reduced with lithium in liquid ammonia in a mixture of THF and a non-polar solvent to a temperature not higher than -33ºC, then a) the hydroxyl group is oxidized in position 20 of (11b, 17a, 20x) -11-methyl-norpregn-5 (10) -en-17,20-diol-3 -one of formula (7) obtained with at least three equivalents of mixture of dimethyl sulfoxide / oxalyl chloride reagents in dichloromethane keeping the temperature below -40ºC, and after adding no more than three equivalents of trialkylamine, the oxidation is continued at a temperature not higher than 0ºC,Acetyl a (11b, 17a) - 17-hydroxi-11-meth-norpregn-5 (10) - en-3, 20-diona de
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