2-[(4aR,5S,6aS,8S,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate -Drug Synthesis Database

【结构式】

【分子编号】38916

【品名】2-[(4aR,5S,6aS,8S,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate

【CA登记号】

【分子式】C₃₂H₄₄O₇

【分子量】540.69716

【元素组成】C 71.08% H 8.2% O 20.71%

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：(Va)

The acylation of 11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione (I) with isobutyric anhydride in pyridine gives the 16,17,21-triester (III), which is condensed with cyclohexanecarbaldehyde (IV) by means of HCl and HClO4 in dioxane yielding the cyclic ketal (Va-b) as a diastereomeric mixture. Finally, this mixture is resolved by preparative HPLC over Lichrosorb RP-18 affording the desired (R)-isomer, the target compound. Alternatively, the monoacylation of the ketal 11beta,16alpha,17alpha,21-tetrahydroxypregan-1,4-diene-3,20-dione 16,17-O-cyclohexylmethylene ketal (VI) with isobutyric anhydride (II) by means of K2CO3 in acetone gives the previously described diastereomeric mixture (Va-b), which is resolved by crystallization in ethanol/water.

参考文献中间体

合成目标

【1】 Calatayud, J.; Conde, J.R.; Luna, M. (Byk Elmu SA); Acetals and esters of 16alpha-hydroxyprednisolone and fluocinolone. BE 1005876; CH 683343; DE 4129535; ES 2034893; FR 2666585; GB 2247680; JP 1992257599; US 5482934 .
【2】 Gutterer, B.; Amschler, H.; Flockerzi, D. (Byk Gulden Lomberg Chemische Fabrik GmbH); Process for R-epimer enrichment of 16,17-acetal derivs. of 21-acyloxy pregnan-1,4-dien-11beta,16alpha,17alpha-triol-3,20-dione derivs.. DE 19635498; WO 9809982 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Va)	38916	2-[(4aR,5S,6aS,8S,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate		C₃₂H₄₄O₇	详情	详情
(Vb)	38917	2-[(4aR,5S,6aS,8R,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate		C₃₂H₄₄O₇	详情	详情
(I)	32675	(8S,9S,10R,11S,13S,14S,16R,17S)-17-glycoloyl-11,16,17-trihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₁H₂₈O₆	详情	详情
(II)	22334	1-methylpropionic anhydride	97-72-3	C₈H₁₄O₃	详情	详情
(III)	38915	2-[(10R,11S,13S,16R,17S)-11-hydroxy-16,17-bis(isobutyryloxy)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 2-methylpropanoate		C₃₃H₄₆O₉	详情	详情
(IV)	33694	cyclohexanecarbaldehyde	2043-61-0	C₇H₁₂O	详情	详情
(VI)	38918	(4aR,5S,6aS,6bS,9aR)-8-cyclohexyl-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one		C₂₈H₃₈O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Pierluigi R,MacDonald P.2007.Improved process for the preparation of ciclesonide. W0 2007056181

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)	22334	1-methylpropionic anhydride	97-72-3	C₈H₁₄O₃	详情	详情
(II)	66190	(6aS,7R,8aR,8bR,11aS,12bR)-7-hydroxy-8b-(2-hydroxyacetyl)-6a,8a,10,10-tetramethyl-6a,6b,7,8,8a,8b,11a,12,12a,12b-decahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-4(2H)-one		C₂₄H₃₂O₆	详情	详情
(III)	66191	(6aR,7S,8aS,8bS,11aR,12bS)-7-hydroxy-8b-isobutyryl-6a,8a,10,10-tetramethyl-6a,6b,7,8,8a,8b,11a,12,12a,12b-decahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-4(2H)-one		C₂₆H₃₆O₅	详情	详情
(IV)	38916	2-[(4aR,5S,6aS,8S,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate		C₃₂H₄₄O₇	详情	详情
(IV)	33694	cyclohexanecarbaldehyde	2043-61-0	C₇H₁₂O	详情	详情

Extended Information