tert-butyl(chloro)dimethylsilane -Drug Synthesis Database

【结构式】

【分子编号】32057

【品名】tert-butyl(chloro)dimethylsilane

【CA登记号】18162-48-6

【分子式】C₆H₁₅ClSi

【分子量】150.7233

【元素组成】C 47.81% H 10.03% Cl 23.52% Si 18.63%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XIX)

The acetylation of (XIII) with acetic anhydride and triethylamine in methylene chloride yields the diacetoxy-bistetra-hydropyranyloxy acetylenic compound (XlV), which by a treatment with Cu2Br2-LiCH3 in ether is converted into 16-phenoxy-9alpha-acetoxy-11alpha,15alpha-bistetrahydropyranyloxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid methyl ester (XV). Elimination of the tetrahydropyranyl groups with acetic acid in water gives the corresponding dihydroxy compound (XVI), which is fully deprotected with K2CO3 in methanol yielding 9alpha,11alpha,15alpha-trihydroxy-16-phenoxy-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid (XVII). The methylation of (XVII) with diazomethane affords the corresponding methyl ester (XVIII), which by treatment with tert-butyldimethylsilyl chloride (XIX) in DMF is converted into the corresponding 11,15-bis(silyloxy) compound (XX). The oxidation of (XX) with CrO3 - pyridine in CH2Cl2 affords 9-oxo-16-phenoxy-11alpha,15alpha-bis(tert-butyldimethylsilyloxy)-17,18,19,20-tetranorprosta-4,5,13-trans-trienoic acid methyl ester (XXI), which is deprotected with aqueous acetic acid giving the free keto ester (XXII). Finally, this ester is hydrolyzed by treatment with pancreatic lipase.

参考文献中间体

合成目标

【1】 Van Horn, A.R.; Garay, G.; Edwards, J.A. (Syntex (USA), Inc.); (dl)-16-Phenoxy- and 16-substituted phenoxy-9-keto prostatrienoic acid derivatives and processes for the production thereof. DE 2927715; EP 0008003; ES 482330; FR 2430939; GB 2025413; US 4178457 .
【2】 Muchowski, J.M.; Fried, J.H. (Syntex (USA), Inc.); 16-Phenoxy and 16-substituted phenoxy-prostatrienoic acid derivatives. DE 2627910; ES 449162; FR 2315263; US 3985791 .
【3】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Hillier, K.; RS-84,135. Drugs Fut 1982, 7, 11, 812.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	32049	methyl 6-hydroxy-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4-heptynoate		C₃₅H₅₀O₉	详情	详情
(XIV)	32050	methyl 6-(acetoxy)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4-heptynoate		C₃₉H₅₄O₁₁	详情	详情
(XV)	32051	methyl 7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3R)-4-phenoxy-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-4,5-heptadienoate		C₃₇H₅₂O₉	详情	详情
(XVI)	32052	methyl 7-[(1R,2R,3R,5S)-5-(acetoxy)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoate		C₂₅H₃₂O₇	详情	详情
(XVII)	32053	7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoic acid		C₂₂H₂₈O₆	详情	详情
(XVIII)	32054	methyl 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-phenoxy-1-butenyl]cyclopentyl]-4,5-heptadienoate		C₂₃H₃₀O₆	详情	详情
(XIX)	32057	tert-butyl(chloro)dimethylsilane	18162-48-6	C₆H₁₅ClSi	详情	详情
(XX)	32055	methyl 7-[(1R,2R,3R,5S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-phenoxy-1-butenyl)-5-hydroxycyclopentyl]-4,5-heptadienoate		C₃₅H₅₈O₆Si₂	详情	详情
(XXI)	32056	methyl 7-[(1R,2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-phenoxy-1-butenyl)-5-oxocyclopentyl]-4,5-heptadienoate		C₃₅H₅₆O₆Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：

Prasterone can be obtained by two related ways: 1) The acetylation of cholesterol (I) with refluxing acetic anhydride gives the corresponding acetate (II), which is brominated with Br2 in acetic acid to the dibromide (III). The oxidation of (III) with CrO3 in acetic acid followed by debromination with Zn in the same solvent and treatment with semicarbazide and sodium acetate in ethanol/water affords 3beta-acetoxyandrost-5-en-17-one semicarbazone (IV), which is finally hydrolyzed with 5N H2SO4 in refluxing ethanol. 2) The partial silylation of androst-5-ene-3beta,17beta-diol (V) with tert-butyldimethylsilyl chloride and imidazole in DMF yields the 3beta-silyloxy derivative (VI), which is oxidized with CrO3-pyridine complex in pyridine affording 3-(tert-butyldimethylsilyloxy)androst-5-en-17-one (VII). Finally, this compound is deprotected with hot acetic acid/water/THF or with tetrabutylammonium fluoride in THF.

参考文献中间体

合成目标

【1】 Fernholz, E.; Wallis, E.S.; The preparation of dehydroandrosterone from cholesterol. J Am Chem Soc 1935, 57, 1504-6.
【2】 Castañer, J.; Mealy, N.; Rabasseda, X.; Prasterone. Drugs Fut 1995, 20, 6, 575.
【3】 Ruzicka, L.; Wettstein, A.; Sexual hormones: Synthetic preparation of the male sexual hormones trans-dehydroandrosterone and androstene-3,17-dione. Helv Chim Acta 1935, 18, 986-95.
【4】 Fernholz, E.; Wallis, E.S.; The constitution of dehydro-androsterone and its preparation from cholesterol. J Am Chem Soc 1935, 57, 1379-80.
【5】 Hosoda, H.; Fishman, J.; Fukushima, D.K.; Convenient, high yield conversion of androst-5-ene-3beta,17beta-diol to dehydroisoandrosterone. J Org Chem 1973, 38, 24, 4209-11.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32057	tert-butyl(chloro)dimethylsilane	18162-48-6	C₆H₁₅ClSi	详情	详情
(I)	16812	(+)-Cholesterol; (+)-(3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-ol	14868-17-8	C₂₇H₄₆O	详情	详情
(II)	16813	(3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate	604-35-3	C₂₉H₄₈O₂	详情	详情
(III)	16814	(3S,8S,9S,10R,13R,14S,17R)-5,6-dibromo-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate		C₂₉H₄₈Br₂O₂	详情	详情
(IV)	16815	(3S,8R,9S,10R,13S,14S)-17-[(E)-2-(aminocarbonyl)hydrazono]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate		C₂₂H₃₃N₃O₃	详情	详情
(V)	16816	(3S,8R,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol; 3beta,17beta-Dihydroxyandrost-5-ene; 5-Androstene-3beta,17beta-diol	521-17-5	C₁₉H₃₀O₂	详情	详情
(VI)	16817	(3S,8R,9S,10R,13S,14S,17S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol		C₂₅H₄₄O₂Si	详情	详情
(VII)	16818	(3S,8R,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one		C₂₅H₄₂O₂Si	详情	详情

Extended Information