(1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate -Drug Synthesis Database

【结构式】

【分子编号】40271

【品名】(1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate

【CA登记号】

【分子式】C₄₆H₈₀F₃NO₄Si₂

【分子量】824.3117496

【元素组成】C 67.03% H 9.78% F 6.91% N 1.7% O 7.76% Si 6.81%

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：(XXXIX)

The O-silylated 4-hydroxy-delta-caprolactam (XXXIV) was reduced with borane and the resulting piperidine was protected as the N-Boc derivative (XXXV). Lithiation employing sec-butyllithium and TMEDA, followed by addition of aldehyde (XXXIII) produced an inseparable 3:1 mixture of the alcohol epimers (XXXVIIa-b) and the trans-oxazolidinone (XXXVI). Acylation of the mixture with m-(trifluoromethyl)benzoyl chloride afforded a diastereomeric mixture of (trifluoromethyl)benzoates (XXXVIIIa-b), separable by column chromatography. Deprotection of the Boc group from the syn-isomer of (XXXVIII) by means of trimethylsilyl triflate and lutidine gave the free amine (XXXIX). Subsequent cyclization of (XXXIX) with AgNO3 afforded the desired cis-quinolizidine (XL) with very high diastereoselectivity. Reductive cleavage of the (trifluoromethyl)benzoyl group of (XL), followed by treatment of the free alcohol with methanesulfonyl chloride provided mesylate (XLI).

参考文献中间体

合成目标

【1】 Ha, J.D.; Cha, J.K.; Total synthesis of clavepictines A and B. Diastereoselective cyclization of delta-aminoallenes. J Am Chem Soc 1999, 121, 43, 10012.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	17346	Benzyloxyacetaldehyde; 2-(Benzyloxy)acetaldehyde	60656-87-3	C₉H₁₀O₂	详情	详情
(XXXVIIa)	40267	tert-butyl (2S,3R,6R)-6-[(1S,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₄₃H₈₅NO₅Si₂	详情	详情
(XXXVIIb)	40268	tert-butyl (2S,3R,6R)-6-[(1R,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₄₃H₈₅NO₅Si₂	详情	详情
(XXXVIIIa)	40269	tert-butyl (2S,3R,6R)-2-methyl-6-[(1S,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₅₁H₈₈F₃NO₆Si₂	详情	详情
(XXXVIIb)	40270	tert-butyl (2S,3R,6R)-2-methyl-6-[(1R,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₅₁H₈₈F₃NO₆Si₂	详情	详情
(XXXIII)	40265	(7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal		C₂₃H₄₄O₂Si	详情	详情
(XXXIV)	40278	(5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]-2-piperidinone		C₁₅H₃₁NO₂Si	详情	详情
(XXXV)	40279	tert-butyl (2S,3R)-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₂₀H₄₁NO₃Si	详情	详情
(XXXVI)	40266	(1R,5S,6R,8aR)-5-methyl-6-[(triisopropylsilyl)oxy]-1-[(6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one		C₃₉H₇₅NO₄Si₂	详情	详情
(XXXIX)	40271	(1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate		C₄₆H₈₀F₃NO₄Si₂	详情	详情
(XL)	40272	(1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl 3-(trifluoromethyl)benzoate		C₄₆H₈₀F₃NO₄Si₂	详情	详情
(XLI)	40273	(1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl methanesulfonate		C₃₉H₇₉NO₅SSi₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIX)

The O-silylated 4-hydroxy-delta-caprolactam (XXXIV) was reduced with borane and the resulting piperidine was protected as the N-Boc derivative (XXXV). Lithiation employing sec-butyllithium and TMEDA, followed by addition of aldehyde (XXXIII) produ-ced an inseparable 3:1 mixture of the alcohol epimers (XXXVIIa-b) and the trans-oxazolidinone (XXXVI). Acylation of the mixture with m-(trifluoromethyl)benzoyl chloride afforded a diastereomeric mixture of (trifluoromethyl)benzoates (XXXVIIIa-b), separable by column chromatography. Deprotection of the Boc group from the syn-isomer of (XXXVIII) by means of trimethylsilyl triflate and lutidine gave the free amine (XXXIX). Subsequent cyclization of (XXXIX) with AgNO3 afforded the desired cis-quinolizidine (XL) with very high diastereoselectivity. Reductive cleavage of the (trifluoromethyl)benzoyl group of (XL), followed by treatment of the free alcohol with methanesulfonyl chloride provided mesylate (XLI).

参考文献中间体

合成目标

【1】 Ha, J.D.; Cha, J.K.; Total synthesis of clavepictines A and B. Diastereoselective cyclization of delta-aminoallenes. J Am Chem Soc 1999, 121, 43, 10012.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13746	3-(Trifluoromethyl)benzoyl chloride	2251-65-2	C₈H₄ClF₃O	详情	详情
(XXXVIIa)	40267	tert-butyl (2S,3R,6R)-6-[(1S,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₄₃H₈₅NO₅Si₂	详情	详情
(XXXVIIb)	40268	tert-butyl (2S,3R,6R)-6-[(1R,7S)-1-hydroxy-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₄₃H₈₅NO₅Si₂	详情	详情
(XXXVIIIa)	40269	tert-butyl (2S,3R,6R)-2-methyl-6-[(1S,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₅₁H₈₈F₃NO₆Si₂	详情	详情
(XXXVIIb)	40270	tert-butyl (2S,3R,6R)-2-methyl-6-[(1R,7S)-1-[[3-(trifluoromethyl)benzoyl]oxy]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl]-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₅₁H₈₈F₃NO₆Si₂	详情	详情
(XXXIII)	40265	(7S)-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienal		C₂₃H₄₄O₂Si	详情	详情
(XXXIV)	40278	(5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]-2-piperidinone		C₁₅H₃₁NO₂Si	详情	详情
(XXXV)	40279	tert-butyl (2S,3R)-2-methyl-3-[(triisopropylsilyl)oxy]-1-piperidinecarboxylate		C₂₀H₄₁NO₃Si	详情	详情
(XXXVI)	40266	(1R,5S,6R,8aR)-5-methyl-6-[(triisopropylsilyl)oxy]-1-[(6S)-6-[(triisopropylsilyl)oxy]-3,4-tridecadienyl]hexahydro[1,3]oxazolo[3,4-a]pyridin-3-one		C₃₉H₇₅NO₄Si₂	详情	详情
(XXXIX)	40271	(1R,7S)-1-[(2R,5R,6S)-6-methyl-5-[(triisopropylsilyl)oxy]piperidinyl]-7-[(triisopropylsilyl)oxy]-4,5-tetradecadienyl 3-(trifluoromethyl)benzoate		C₄₆H₈₀F₃NO₄Si₂	详情	详情
(XL)	40272	(1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl 3-(trifluoromethyl)benzoate		C₄₆H₈₀F₃NO₄Si₂	详情	详情
(XLI)	40273	(1R,4S,6S,7R,9aR)-6-methyl-7-[(triisopropylsilyl)oxy]-4-[(E,3S)-3-[(triisopropylsilyl)oxy]-1-decenyl]octahydro-2H-quinolizin-1-yl methanesulfonate		C₃₉H₇₉NO₅SSi₂	详情	详情

Extended Information