(1aS,3aS,6aR,6bR)-3a-methyloctahydro-4H-indeno[4,5-b]oxiren-4-one -Drug Synthesis Database

【结构式】

【分子编号】45538

【品名】(1aS,3aS,6aR,6bR)-3a-methyloctahydro-4H-indeno[4,5-b]oxiren-4-one

【CA登记号】

【分子式】C₁₀H₁₄O₂

【分子量】166.21996

【元素组成】C 72.26% H 8.49% O 19.25%

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：(VII)

The indenone intermediate (XIII) has been obtained as follows: The silylation of 3-methyl-1-pentyn-3-ol (I) with Tes-Cl and DMAP in DMF gives the silyl ether (II), which is condensed with paraformaldehyde and n-BuLi in THF to yield the propargyl alcohol (III). Partial reduction of (III) with Red-Al in THF affords the allyl alcohol (IV), which is treated with Ts-Cl and DMAP in dichloromethane to provide the allyl chloride (V). The condensation of (V) with the unsaturated ester (VI) (obtained by Wittig condensation of perhydroindanone (VII) with triethyl phosphonoacetate (VIII) by means of EtONa) by means of BuLi and dicyclohexylamine in HMPA gives the octenoic ester (IX), which is reduced with LiAlH4, yielding the corresponding primary alcohol (X). The reaction of (X) with TsCl and pyridine affords the tosylate (XI), which is reduced with LiBEt3H in THF with simultaneous opening of the epoxide ring to provide the hexahydroindenol (XII). Finally, this compound is oxidized with pyridinium dichromate (PDC), yielding the target hexahydroindenone intermediate (XIII).

参考文献中间体

合成目标

【1】 Radinov, R.N.; Daniewski, A.R. (F. Hoffmann-La Roche AG); Process for preparing anti-osteoporotic agents. EP 1048661; JP 2000336094 .

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)	46664	3-ethyl-1-pentyn-3-ol	6285-06-9	C₇H₁₂O	详情	详情
(II)	46665	[(1,1-diethyl-2-propynyl)oxy](triethyl)silane; 1,1-diethyl-2-propynyl triethylsilyl ether		C₁₃H₂₆OSi	详情	详情
(III)	46666	4-ethyl-4-[(triethylsilyl)oxy]-2-hexyn-1-ol		C₁₄H₂₈O₂Si	详情	详情
(IV)	46667	(E)-4-ethyl-4-[(triethylsilyl)oxy]-2-hexen-1-ol		C₁₄H₃₀O₂Si	详情	详情
(V)	46668	(E)-4-chloro-1,1-diethyl-2-butenyl triethylsilyl ether; [[(E)-4-chloro-1,1-diethyl-2-butenyl]oxy](triethyl)silane		C₁₄H₂₉ClOSi	详情	详情
(VI)	46669	ethyl 2-[(1aS,3aS,6aR,6bR)-3a-methyloctahydro-4H-indeno[4,5-b]oxiren-4-ylidene]acetate		C₁₄H₂₀O₃	详情	详情
(VII)	45538	(1aS,3aS,6aR,6bR)-3a-methyloctahydro-4H-indeno[4,5-b]oxiren-4-one		C₁₀H₁₄O₂	详情	详情
(VIII)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(IX)	46670	ethyl (2S,4E)-2-[(1aS,3aS,6aR,6bR)-3a-methyl-2,3,3a,6,6a,6b-hexahydro-1aH-indeno[4,5-b]oxiren-4-yl]-6-ethyl-6-[(triethylsilyl)oxy]-4-octenoate		C₂₈H₄₈O₄Si	详情	详情
(X)	46671	(3aS,7S,7aR)-3-[(1S,3E)-5-ethyl-1-(hydroxymethyl)-5-[(triethylsilyl)oxy]-3-heptenyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-ol		C₂₆H₄₈O₃Si	详情	详情
(XI)	46672	(2S,4E)-2-[(3aS,7S,7aR)-7-hydroxy-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]-6-ethyl-6-[(triethylsilyl)oxy]-4-octenyl 4-methylbenzenesulfonate		C₃₃H₅₄O₅SSi	详情	详情
(XII)	46673	(3aS,7S,7aR)-3-[(1S,3E)-5-ethyl-1-methyl-5-[(triethylsilyl)oxy]-3-heptenyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-ol		C₂₆H₄₈O₂Si	详情	详情
(XIII)	46674	(3aR,7aS)-1-[(1S,3E)-5-ethyl-1-methyl-5-[(triethylsilyl)oxy]-3-heptenyl]-7a-methyl-3,3a,5,6,7,7a-hexahydro-4H-inden-4-one		C₂₆H₄₆O₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

The bromination of the Hajos dione (XI) with t-Bu-Cu, DIBAL and Br2 in HMPA/THF gives the bromo derivative (XII), which is reduced with LiAlH(t-BuO)3 in THF to yield the diol (XIII). The dehydrobromination of (XIII) with KH in HMPA affords the epoxide (XIV), which is oxidized with pyridinium dichromate (PDC) in dichloromethane to provide the ketoepoxide (XV). The Wittig condensation of (XV) with phosphonium salt (XVI) by means of potassium tert-butoxide gives the ethylidene epoxide (XVII), which is finally opened with LiAlH4 in THF to yield the target intermediate (I).

参考文献中间体

合成目标

【1】 Liu, W.; Daniewski, A.R.; A novel silycopper catalyst for the reductivo bromination of hajos dione. Improved preparation of a CD synthon for teh synthesis of vitamin D. J Org Chem 2001, 66, 2, 626.

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)	42566	(3aR,4S,7aS)-1-[(Z)ethylidene]-7a-methyloctahydro-1H-inden-4-ol		C₁₂H₂₀O	详情	详情
(XI)	45534	(7aS)-7a-methyl-2,3,7,7a-tetrahydro-1H-indene-1,5(6H)-dione	17553-86-5	C₁₀H₁₂O₂	详情	详情
(XII)	45535	(3aR,4S,7aS)-4-bromo-7a-methylhexahydro-1H-indene-1,5(4H)-dione	2706-38-9	C₁₀H₁₃BrO₂	详情	详情
(XIII)	45536	(1S,3aR,4S,5S,7aS)-4-bromo-7a-methyloctahydro-1H-indene-1,5-diol		C₁₀H₁₇BrO₂	详情	详情
(XIV)	45537	(1aS,3aS,4S,6aR,6bR)-3a-methyloctahydro-1aH-indeno[4,5-b]oxiren-4-ol		C₁₀H₁₆O₂	详情	详情
(XV)	45538	(1aS,3aS,6aR,6bR)-3a-methyloctahydro-4H-indeno[4,5-b]oxiren-4-one		C₁₀H₁₄O₂	详情	详情
(XVI)	11717	Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide	1530-32-1	C₂₀H₂₀BrP	详情	详情
(XVII)	45539	(1aS,3aS,6aR,6bR)-4-[(Z)ethylidene]-3a-methyloctahydro-4H-indeno[4,5-b]oxirene		C₁₂H₁₈O	详情	详情

Extended Information