3,5-bis(acetoxy)cyclohexyl acetate -Drug Synthesis Database

【结构式】

【分子编号】49040

【品名】3,5-bis(acetoxy)cyclohexyl acetate

【CA登记号】

【分子式】C₁₂H₁₈O₆

【分子量】258.27132

【元素组成】C 55.81% H 7.02% O 37.17%

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：(II)

The reaction of cis,cis-cyclohexane-1,3,5-triol (I) with Ac2O and pyridine gives the triacetate (II), which is monodeacylated by means of porcine liver esterase at pH 7 to yield the diacetate (III). The silylation of the OH group of (III) with Tbdms-Cl , TEA and DMAP in dichloromethane affords the silyl ether (IV), which is submitted to desymmetrization by enzymatic hydrolysis with porcine liver esterase to provide the chiral cyclohexanol derivative (V). The oxidation of (V) by means of PCC in dichloromethane gives the chiral cyclohexanone (VI), which is finally treated with DBU in dichloromethane to yield the intermediate 5(S)-(Tbdms-O)-2-cyclohexenone (VII).

参考文献中间体

合成目标

【1】 Kalkote, U.R.; et al.; Simple, efficient chemoenzymatic synthesis of (S)-5-(tert-butyldimethylsilyloxy)-2-cyclohexenone and enantiomeric ketone intermediates of 19-Nor-1alpha,25-dihydroxyvitamin D3. J Org Chem 2001, 66, 24, 8277.

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)	11800	1,3,5-Cyclohexanetriol; cis,cis-1,3,5-Cyclohexanetriol dihydrate	50409-12-6	C₆H₁₂O₃	详情	详情
(II)	49040	3,5-bis(acetoxy)cyclohexyl acetate		C₁₂H₁₈O₆	详情	详情
(III)	57152	(1R,3S)-3-(acetyloxy)-5-hydroxycyclohexyl acetate		C₁₀H₁₆O₅	详情	详情
(IV)	57153	(1R,3S)-3-(acetyloxy)-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl acetate		C₁₆H₃₀O₅Si	详情	详情
(V)	57154	(1S,3R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxycyclohexyl acetate		C₁₄H₂₈O₄Si	详情	详情
(VI)	57155	(1R,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-oxocyclohexyl acetate		C₁₄H₂₆O₄Si	详情	详情
(VII)	57138	(5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one		C₁₂H₂₂O₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

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.

参考文献中间体

合成目标

【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