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【结 构 式】

【分子编号】49038

【品名】(Z)-10,10,10-trifluoro-5,5-dimethyl-9-[(triethylsilyl)oxy]-9-(trifluoromethyl)-7-decenal

【CA登记号】

【 分 子 式 】C19H32F6O2Si

【 分 子 量 】434.5377992

【元素组成】C 52.52% H 7.42% F 26.23% O 7.36% Si 6.46%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IX)

Synthesis of aldehyde intermediate (IX): The condensation of 1-tert-butoxy-4-chlorobutane (I) with 4-methyl-3-penten-2-one (II) by means of Mg in hot THF gives the 2-octanone (III), which is condensed with hexafluoroacetone (IV) by means of diethyl chlorophosphate and LDA in THF to yield the fluorinated alkynol (V). Hydrogenation of the triple bond of (V) with H2 and Lindlar catalyst affords the cis-alkene (VI), which is deprotected with sulfuric acid to provide the fluorinated diol (VII). Finally, the primary alcohol of (VII) is oxidized to the corresponding aldehyde (VIII) with NaOCl and tempo, which is silylated with Tes-Cl and TEA to afford the desired intermediate (IX).

1 Wirz, B.; Hilpert, H.; Novel versatile approach to an enantiopure 19-nor, des-C,D vitamin D-3 derivative. Tetrahedron 2001, 57, 4, 681.
2 Hilpert, H.; Wirz, B. (F. Hoffmann-La Roche AG); New process for the preparation of retiferol derivs.. EP 1094060 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 49032 tert-butyl 4-chlorobutyl ether; 1-(tert-butoxy)-4-chlorobutane C8H17ClO 详情 详情
(II) 42266 4-methyl-3-penten-2-one 141-79-7 C6H10O 详情 详情
(III) 49033 8-(tert-butoxy)-4,4-dimethyl-2-octanone C14H28O2 详情 详情
(IV) 44260 1,1,1,3,3,3-hexafluoroacetone 684-16-2 C3F6O 详情 详情
(V) 49034 10-(tert-butoxy)-1,1,1-trifluoro-6,6-dimethyl-2-(trifluoromethyl)-3-decyn-2-ol C17H26F6O2 详情 详情
(VI) 49035 (Z)-10-(tert-butoxy)-1,1,1-trifluoro-6,6-dimethyl-2-(trifluoromethyl)-3-decen-2-ol C17H28F6O2 详情 详情
(VII) 49036 (Z)-10,10,10-trifluoro-5,5-dimethyl-9-(trifluoromethyl)-7-decene-1,9-diol C13H20F6O2 详情 详情
(VIII) 49037 (Z)-10,10,10-trifluoro-9-hydroxy-5,5-dimethyl-9-(trifluoromethyl)-7-decenal C13H18F6O2 详情 详情
(IX) 49038 (Z)-10,10,10-trifluoro-5,5-dimethyl-9-[(triethylsilyl)oxy]-9-(trifluoromethyl)-7-decenal C19H32F6O2Si 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IX)

The hydrogenation of 1,3,5-trihydroxybenzene (X) with H2 over Raney-Ni gives a mixture of the cis-triol (XI) and the trans-triol (XII), which is submitted to a thermal isomerization to obtain a trans-enriched mixture. The acetylation of (XI) + (XII) with acetic anhydride and pyridine affords the mixture of triacetates (XIII) + (XIV), which is submitted to a selective deacetylation by means of Lipase OF (isolated from Candida rugosa) to provide the enantiomerically pure diacetate (XV). The oxidation of (XV) with NaOCl and tempo in dichloromethane/water gives the chiral ketone (XVI), which is condensed with ethyl 2-(trimethylsilyl)acetate (XVII) by means of LDA in THF to yield the cyclohexylideneacetate (XVIII). The deacetylation of (XVIII) by means of K2CO3 in methanol/water affords the chiral dihydroxy compound (XIX), which is protected with Tbdms-Cl and imidazole to provide the bis-silyl ether (XX). The reduction of the ester group of (XX) with Red-Al in toluene furnishes the allyl alcohol (XXI), which is treated with TsCl and n-BuLi to obtain the tosylate (XXII). The reaction of (XXII) with diphenylphosphine and BuLi in THF gives the phosphinoxide (XXIII), which is condensed with the intermediate aldehyde (IX) by means of BuLi in THF to yield the silylated precursor (XXIV). Finally, this compound is desilylated by means of TBAF in THF.

1 Wirz, B.; Hilpert, H.; Novel versatile approach to an enantiopure 19-nor, des-C,D vitamin D-3 derivative. Tetrahedron 2001, 57, 4, 681.
2 Hilpert, H.; Wirz, B. (F. Hoffmann-La Roche AG); New process for the preparation of retiferol derivs.. EP 1094060 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IX) 49038 (Z)-10,10,10-trifluoro-5,5-dimethyl-9-[(triethylsilyl)oxy]-9-(trifluoromethyl)-7-decenal C19H32F6O2Si 详情 详情
(X) 11799 1,3,5-Benzenetriol; Fluoroglucinol 108-73-6 C6H6O3 详情 详情
(XI) 11800 1,3,5-Cyclohexanetriol; cis,cis-1,3,5-Cyclohexanetriol dihydrate 50409-12-6 C6H12O3 详情 详情
(XII) 49039 1,3,5-cyclohexanetriol C6H12O3 详情 详情
(XIII) 49040 3,5-bis(acetoxy)cyclohexyl acetate C12H18O6 详情 详情
(XIV) 49041 3,5-bis(acetoxy)cyclohexyl acetate C12H18O6 详情 详情
(XV) 49042 (1R,3R)-3-(acetoxy)-5-hydroxycyclohexyl acetate C10H16O5 详情 详情
(XVI) 49043 (1S,3S)-3-(acetoxy)-5-oxocyclohexyl acetate C10H14O5 详情 详情
(XVII) 49044 ethyl 2-(trimethylsilyl)acetate C7H16O2Si 详情 详情
(XVIII) 49045 ethyl 2-[(3R,5R)-3,5-bis(acetoxy)cyclohexylidene]acetate C14H20O6 详情 详情
(XIX) 49046 ethyl 2-[(3R,5R)-3,5-dihydroxycyclohexylidene]acetate C10H16O4 详情 详情
(XX) 49047 ethyl 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)acetate C22H44O4Si2 详情 详情
(XXI) 49048 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)-1-ethanol C20H42O3Si2 详情 详情
(XXII) 49049 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl 4-methylbenzenesulfonate C27H48O5SSi2 详情 详情
(XXIII) 30302 [2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl(diphenyl)phosphine oxide C32H51O3PSi2 详情 详情
(XXIV) 49050 [[(2Z,9E)-11-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)-5,5-dimethyl-1,1-bis(trifluoromethyl)-2,9-undecadienyl]oxy](triethyl)silane; (2Z,9E)-11-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)-5,5-dimethyl-1,1-bis(trifluoromethyl)-2,9-undecadienyl triethylsilyl ether C39H72F6O3Si3 详情 详情
Extended Information