(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone -Drug Synthesis Database

【结构式】

【分子编号】21732

【品名】(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone

【CA登记号】

【分子式】C₂₂H₃₅NO₃Si

【分子量】389.61034

【元素组成】C 67.82% H 9.05% N 3.6% O 12.32% Si 7.21%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(IV)

Lithium enolate (II), generated from chiral ester (I) and LDA at -84 C, was cyclocondensed with imine (III) to furnish azetidinone (IV). The N-p-methoxyphenyl group of (IV) was then removed by oxidative treatment with ceric ammonium nitrate at -10 C, and the resulting azetidinone (V) was protected with Boc2O to afford tert-butyl carbamate (VI).

参考文献中间体

合成目标

【1】 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.
【2】 Takahashi, N.; et al.; Growth inhibition of gastric cancer cells by troglitazone, a ligand for peroxisome proliferator-activated receptor. Dig Dis Week (May 16 1999, Orlando) 1999, Abst 3684.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	21730	2-(Triisopropylsilyloxy)-1-(2(S)-phenyl-1(R)-cyclohexyl)vinyl-1-ol lithium salt	C₂₃H₃₇LiO₃Si	详情	详情
(IV)	21732	(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₂H₃₅NO₃Si	详情	详情
(V)	19156	(3R,4S)-4-(2-methyl-1-propenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₁₆H₃₁NO₂Si	详情	详情
(VI)	19157	tert-butyl (2S,3R)-2-(2-methyl-1-propenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate	C₂₁H₃₉NO₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Lithium enolate (II), generated from chiral ester (I) and LDA at -84 C, was cyclocondensed with imine (III) to furnish azetidinone (IV). After removal of the triisopropylsilyl group of (IV) using HF in pyridine, the resulting lactam was treated with CH2I2 and Et2Zn in 1,2-dichloroethane to give the dimethylcyclopropyl azetidinone (V). The C-3 hydroxyl group was reprotected as the triisopropylsilyl ether (VI). Then, the N-p-methoxyphenyl group of (VI) was removed by oxidative treatment with ceric ammonium nitrate at -10 C, and the resulting azetidinone was N-protected with Boc2O to afford tert-butyl carbamate (VII).

参考文献中间体

合成目标

【1】 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	21730	2-(Triisopropylsilyloxy)-1-(2(S)-phenyl-1(R)-cyclohexyl)vinyl-1-ol lithium salt	C₂₃H₃₇LiO₃Si	详情	详情
(IV)	21732	(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₂H₃₅NO₃Si	详情	详情
(V)	21741	(3R,4S)-4-[(1S)-2,2-dimethylcyclopropyl]-3-hydroxy-1-(4-methoxyphenyl)-2-azetidinone	C₁₅H₁₉NO₃	详情	详情
(VI)	21742	(3R,4S)-4-[(1S)-2,2-dimethylcyclopropyl]-1-(4-methoxyphenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₄H₃₉NO₃Si	详情	详情
(VII)	21743	tert-butyl (2S,3R)-2-[(1S)-2,2-dimethylcyclopropyl]-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate	C₂₂H₄₁NO₄Si	详情	详情

合成路线3

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】 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	19151	(1R,2S)-2-phenylcyclohexyl 2-[(triisopropylsilyl)oxy]acetate	C₂₃H₃₈O₃Si	详情	详情
(II)	21730	2-(Triisopropylsilyloxy)-1-(2(S)-phenyl-1(R)-cyclohexyl)vinyl-1-ol lithium salt	C₂₃H₃₇LiO₃Si	详情	详情
(IV)	21732	(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₂H₃₅NO₃Si	详情	详情
(V)	21741	(3R,4S)-4-[(1S)-2,2-dimethylcyclopropyl]-3-hydroxy-1-(4-methoxyphenyl)-2-azetidinone	C₁₅H₁₉NO₃	详情	详情
(VI)	21742	(3R,4S)-4-[(1S)-2,2-dimethylcyclopropyl]-1-(4-methoxyphenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₄H₃₉NO₃Si	详情	详情
(VII)	21743	tert-butyl (2S,3R)-2-[(1S)-2,2-dimethylcyclopropyl]-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate	C₂₂H₄₁NO₄Si	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

Lithium enolate (II), generated from chiral ester (I) and LDA at -84 C, was cyclocondensed with imine (III) to furnish azetidinone (IV). Ozonolysis of the olefinic bond of (IV) at -78 C in CH2Cl2-MeOH, followed by reductive workup using Me2S afforded aldehyde (V). Subsequent treatment of (V) with diethylaminosulfur trifluoride in CH2Cl2 at r.t. yielded the difluoromethyl lactam (VI). Then, the N-p-methoxyphenyl group of (VI) was removed by oxidative treatment with ceric ammonium nitrate at -5 C, and the resulting azetidinone was N-protected with Boc2O to afford tert-butyl carbamate (VII)

参考文献中间体

合成目标

【1】 Lin, S.; et al.; Syntheses and biological activity of advanced second-generation taxoids. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 315.
【2】 Ferlini, C.; Scambia, G.; Lin, S.; Bernacki, R.J.; Ojima, I.; Wang, T.; Pera, P.; Slater, J.C.; Syntheses and biological activity of C3'-difluoromethyl taxoids. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 39.
【3】 Pera, P.; Scambia, G.; Ojima, I.; Lin, S.; Wang, T.; Ferlini, C.; Slater, J.C.; Bernacki, R.J.; Syntheses and biological activity of C-3'-difluoromethyl-taxoids. Bioorg Med Chem Lett 2000, 8, 7, 1619.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	19151	(1R,2S)-2-phenylcyclohexyl 2-[(triisopropylsilyl)oxy]acetate	C₂₃H₃₈O₃Si	详情	详情
(II)	21730	2-(Triisopropylsilyloxy)-1-(2(S)-phenyl-1(R)-cyclohexyl)vinyl-1-ol lithium salt	C₂₃H₃₇LiO₃Si	详情	详情
(III)	19154	4-methoxy-N-[(E)-3-methyl-2-butenylidene]aniline; N-(4-methoxyphenyl)-N-[(E)-3-methyl-2-butenylidene]amine	C₁₂H₁₅NO	详情	详情
(IV)	21732	(3R,4S)-1-(4-methoxyphenyl)-4-[(E)-1-propenyl]-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₂H₃₅NO₃Si	详情	详情
(V)	21733	(2R,3R)-1-(4-methoxyphenyl)-4-oxo-3-[(triisopropylsilyl)oxy]-2-azetidinecarbaldehyde	C₂₀H₃₁NO₄Si	详情	详情
(VI)	21734	(3R,4R)-4-(difluoromethyl)-1-(4-methoxyphenyl)-3-[(triisopropylsilyl)oxy]-2-azetidinone	C₂₀H₃₁F₂NO₃Si	详情	详情
(VII)	21735	tert-butyl (2R,3R)-2-(difluoromethyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate	C₁₈H₃₃F₂NO₄Si	详情	详情

Extended Information