(1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidinyl]propyl acetate -Drug Synthesis Database

【结构式】

【分子编号】42152

【品名】(1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidinyl]propyl acetate

【CA登记号】

【分子式】C₂₆H₂₃F₂NO₄

【分子量】451.4697664

【元素组成】C 69.17% H 5.13% F 8.42% N 3.1% O 14.18%

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：(III)

By condensation of D-glucopyranuronic acid methyl ester (I) with (3R,4S)-3-[3-acetoxy-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)azetidin-2-one (III) by means of Tms-OTf.

参考文献中间体

合成目标

【1】 Taraporewala, I.B.; Kauffman, J.M.; Synthesis and structure activity relationships of anti-inflammatory 9,10-dihydro-9-oxo-2-acridine-alkanoic acids and 4-(2-carboxyphenyl)aminobenzenealkanoic acids. J Pharm Sci 1990, 79, 2, 173.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	42779	methyl (2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-hydroxytetrahydro-2H-pyran-2-carboxylate	C₁₃H₁₈O₁₀	详情	详情
(II)	42780	(trimethylsilyl)[(2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl]oxonium trifluoromethanesulfonate	C₁₇H₂₇F₃O₁₃SSi	详情	详情
(III)	42152	(1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidinyl]propyl acetate	C₂₆H₂₃F₂NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Diol (III) was acetylated with Ac2O in the presence of dimethylaminopyridine to yield diester (IV), which was selectively hydrolyzed to monoacetate (V) by means of methanolic guanidine. Coupling of phenol (V) with imidate (II) by means of boron trifluoride etherate furnished the protected glucuronide (VI). The ester groups of (VI) were finally hydrolyzed by treatment with triethylamine in aqueous methanol.

参考文献中间体

合成目标

【1】 Yumibe, N.P.; Alton, K.B.; Van Heek, M.; Davis, H.R.; Vaccaro, W.D. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. EP 0877750; JP 1998512592; WO 9716455 .
【2】 Yumibe, N.P.; Alton, K.B.; Vaccaro, W.D.; Davis, H.R.; Van Heek, M. (Schering Corp.); Sugar-substd. 2-azetidinones useful as hypocholesterolemic agents. US 5756470 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	42149	methyl (2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-[(2,2,2-trichloroethanimidoyl)oxy]tetrahydro-2H-pyran-2-carboxylate	C₁₅H₁₈Cl₃NO₁₀	详情	详情
(III)	42150	(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-2-azetidinone	C₂₄H₂₁F₂NO₃	详情	详情
(IV)	42151	4-[(2S,3R)-3-[(3S)-3-(acetoxy)-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]phenyl acetate	C₂₈H₂₅F₂NO₅	详情	详情
(V)	42152	(1S)-1-(4-fluorophenyl)-3-[(2S,3R)-1-(4-fluorophenyl)-2-(4-hydroxyphenyl)-4-oxoazetidinyl]propyl acetate	C₂₆H₂₃F₂NO₄	详情	详情
(VI)	42153	methyl (2S,3R,4S,5R,6S)-3,4,5-tris(acetoxy)-6-[4-[(2S,3R)-3-[(3S)-3-(acetoxy)-3-(4-fluorophenyl)propyl]-1-(4-fluorophenyl)-4-oxoazetidinyl]phenoxy]tetrahydro-2H-pyran-2-carboxylate	C₃₉H₃₉F₂NO₁₃	详情	详情

Extended Information