benzyl 3-(2-chloro-2-oxoethyl)benzoate -Drug Synthesis Database

【结构式】

【分子编号】50932

【品名】benzyl 3-(2-chloro-2-oxoethyl)benzoate

【CA登记号】

【分子式】C₁₆H₁₃ClO₃

【分子量】288.73012

【元素组成】C 66.56% H 4.54% Cl 12.28% O 16.62%

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 precursor acid chloride (VII) was synthesized from isophthalic acid (I) as follows: Treatment of the triethylammonium salt of (I) with benzyl bromide provided the mono-benzyl ester (II). Acid chloride (III) was then formed by reaction of (II) with oxalyl chloride in the presence of a catalytic amount of DMF. Arndt-Eistert homologation of (III) to produce (VI) was achieved via reaction with diazomethane to yield the intermediate diazo ketone (IV). Wolff rearrangement of diazo ketone (IV) in the presence of Ag2O in hot trichloroethanol furnished the trichloroethyl ester (V). Reductive cleavage of the trichloroethyl ester group of (V) with Zn and HOAc then gave the carboxylic acid (VI). This was subsequently activated as the acid chloride (VII) by using oxalyl chloride and DMF.

参考文献中间体

合成目标

【1】 Adlington, R.M.; Baldwin, J.E.; Becker, G.W.; et al.; Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen. J Med Chem 2001, 44, 10, 1491.

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)	50926	m-Phthalic acid; Isophthalic acid; Benzene-1,3-dicarboxylic acid; 1,3-Benzenedicarboxylic acid	121-91-5	C₈H₆O₄	详情	详情
(II)	50927	3-[(benzyloxy)carbonyl]benzoic acid		C₁₅H₁₂O₄	详情	详情
(III)	50928	benzyl 3-(chlorocarbonyl)benzoate		C₁₅H₁₁ClO₃	详情	详情
(IV)	50929			C₁₆H₁₄N₂O₃	详情	详情
(V)	50930	benzyl 3-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]benzoate		C₁₈H₁₅Cl₃O₄	详情	详情
(VI)	50931	2-[3-[(benzyloxy)carbonyl]phenyl]acetic acid		C₁₆H₁₄O₄	详情	详情
(VII)	50932	benzyl 3-(2-chloro-2-oxoethyl)benzoate		C₁₆H₁₃ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The homochiral azetidinone (IX) was prepared from the known beta-lactam (VIII) by N-silylation with tert-butyldimethylsilyl chloride followed by catalytic hydrogenolysis of the benzyl ester. The 3-silylated azetidinone intermediate (X) was obtained by treatment of the lithium enolate of (IX) with trimethylsilyl chloride. Subsequent Peterson reaction of (X) with the 4-silyloxybenzaldehyde (XI) and LDA furnished olefin (XII) as a mixture of geometric isomers. After esterification of the carboxylate group of (XII) with benzyl alcohol in the presence of EDC to yield (XIII), the catalytic hydrogenation of the olefin double bond of (XIII) gave rise to the cis-azetidinone (XIV). The N-tert-butyldimethylsilyl group of (XIV) was selectively removed by treatment with HF in acetonitrile to afford (XV). Acylation of the lactam N of (XV) with acid chloride (VII) in the presence of sodium hexamethyldisilazide provided (XVI). The remaining silyl group of (XVI) was finally removed by treatment with ammonium hydrogen difluoride in NMP-DMF.

参考文献中间体

合成目标

【1】 Adlington, R.M.; Baldwin, J.E.; Becker, G.W.; et al.; Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen. J Med Chem 2001, 44, 10, 1491.
【2】 Chen, B.; Adlington, R.M.; Baldwin, J.E.; et al.; Design and synthesis of novel monocyclic beta-lactam inhibitors of prostate specific antigen. Bioorg Med Chem Lett 1997, 7, 13, 1689.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIa)	50935	(2S)-1-[tert-butyl(dimethyl)silyl]-3-[(Z)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylic acid		C₃₃H₄₁NO₄Si₂	详情	详情
(XIIb)	50936	(2S)-1-[tert-butyl(dimethyl)silyl]-3-[(E)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylic acid		C₃₃H₄₁NO₄Si₂	详情	详情
(XIIIa)	50937	benzyl (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(Z)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylate		C₄₀H₄₇NO₄Si₂	详情	详情
(XIIIb)	50938	benzyl (2S)-1-[tert-butyl(dimethyl)silyl]-3-[(E)-(4-[[tert-butyl(diphenyl)silyl]oxy]phenyl)methylidene]-4-oxo-2-azetidinecarboxylate		C₄₀H₄₇NO₄Si₂	详情	详情
(VII)	50932	benzyl 3-(2-chloro-2-oxoethyl)benzoate		C₁₆H₁₃ClO₃	详情	详情
(VIII)	50942	(S)-Benzyl 2-azetidinone-4-carboxylate; Benzyl (S)-4-oxo-2-azetidinecarboxylate	72776-05-7	C₁₁H₁₁NO₃	详情	详情
(IX)	49426	(2S)-1-[tert-butyl(dimethyl)silyl]-4-oxo-2-azetidinecarboxylic acid		C₁₀H₁₉NO₃Si	详情	详情
(X)	50933	lithium (2R)-1-[tert-butyl(dimethyl)silyl]-4-oxo-3-(trimethylsilyl)-2-azetidinecarboxylate		C₁₃H₂₆LiNO₃Si₂	详情	详情
(XI)	50934	4-[[tert-butyl(diphenyl)silyl]oxy]benzaldehyde		C₂₃H₂₄O₂Si	详情	详情
(XIV)	50939	benzyl (2S,3S)-1-[tert-butyl(dimethyl)silyl]-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate		C₄₀H₄₉NO₄Si₂	详情	详情
(XV)	50940	benzyl (2S,3S)-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate		C₃₄H₃₅NO₄Si	详情	详情
(XVI)	50941	benzyl (2S,3S)-1-(2-[3-[(benzyloxy)carbonyl]phenyl]acetyl)-3-(4-[[tert-butyl(diphenyl)silyl]oxy]benzyl)-4-oxo-2-azetidinecarboxylate		C₅₀H₄₇NO₇Si	详情	详情

Extended Information