methyl 2-(5-chloro-2-methoxyphenyl)acetate -Drug Synthesis Database

【结构式】

【分子编号】39341

【品名】methyl 2-(5-chloro-2-methoxyphenyl)acetate

【CA登记号】

【分子式】C₁₀H₁₁ClO₃

【分子量】214.64824

【元素组成】C 55.96% H 5.17% Cl 16.52% O 22.36%

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：(IV)

The reaction of the taxane derivative (I) with trifluoromethanesulfonic anhydride gives the monotriflate (II), which is treated with sodium azide in hot acetonitrile to yield the cyclopropa derivative (III). The cleavage of the oxazolidine ring of (III) by means of formic acid affords the 3-amino-2-hydroxy derivative (IV), which is finally acylated with tert-butoxycarbonyl anhydride to provide the target taxoid derivative.

参考文献中间体

合成目标

【1】 Bouchard, H.; Buourzat, J.-D.; Commercon, A. (Aventis Pharma SA); Novel taxoids, preparation thereof and pharmaceutical compsns. containing same. EP 0673372; FR 2698871; JP 1996504425; JP 1998291930; US 5814658; WO 9413654 .
【2】 Renard, A.; Bissery, M.-C. (Aventis Pharma SA); Method for treating abnormal cell proliferation in the brain. US 6156789 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	49338	5-[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl] 3-(tert-butyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate	C₄₈H₅₉NO₁₅	详情	详情
(II)	49339	5-((1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(trifluoromethyl)sulfonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl) 3-(tert-butyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate	C₄₉H₅₈F₃NO₁₇S	详情	详情
(III)	49340	5-[(1S,2S,3R,4S,7R,9S,11R,13R,16S)-4,13-bis(acetoxy)-2-(benzoyloxy)-1-hydroxy-15,18,18-trimethyl-12-oxo-6-oxapentacyclo[12.3.1.0(3,11).0(4,7).0(9,11)]octadec-14-en-16-yl] 3-(tert-butyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate	C₄₈H₅₇NO₁₄	详情	详情
(IV)	39341	methyl 2-(5-chloro-2-methoxyphenyl)acetate	C₁₀H₁₁ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

A chiral process for the synthesis of the title compound was later reported. Chlorination of 2-methoxyphenylacetic acid (VII) with sulfuryl chloride gave (VIII), which was further converted to the corresponding methyl ester (IX) by treatment with dimethyl sulfate and K2CO3. Conversion of (IX) to the lithium enolate with lithium hexamethyldisilazide, followed by condensation with aryl fluoride (X) yielded the diarylacetic ester (XI). This was reacted with N-fluoro-bis(phenylsulfonyl)amine to provide fluoro ester (XII). Basic hydrolysis afforded the racemic carboxylic acid (XIII), which was resolved via conversion to the diastereoisomeric salts with (S)-alpha-methylbenzylamine. Reduction of the nitro group from the desired (S)-enantiomer (XIV), and subsequent acidic treatment then produced the title oxindole derivative.

参考文献中间体

合成目标

【1】 Hewawasam, P.; et al.; The synthesis and characterization of BMS-204352 (MaxiPost) and related 3-fluorooxindoles as openers of maxi-K potassium channels. Bioorg Med Chem Lett 2002, 12, 7, 1023.
【2】 Martín, L.; Castañer, R.M.; Sorbera, L.A.; Castañer, J.; BMS-204352. Drugs Fut 2001, 26, 1, 9.
【3】 Thottathil, J.K.; Pendri, Y.R.; Martinez, E.J.; Hewawasam, P. (Bristol-Myers Squibb Co.); Preparation of 3-fluoro oxindole derivs.. WO 9816222 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	19706	2-(2-methoxyphenyl)acetic acid	93-25-4	C₉H₁₀O₃	详情	详情
(VIII)	39340	2-(5-chloro-2-methoxyphenyl)acetic acid		C₉H₉ClO₃	详情	详情
(IX)	39341	methyl 2-(5-chloro-2-methoxyphenyl)acetate		C₁₀H₁₁ClO₃	详情	详情
(X)	39342	1-fluoro-2-nitro-4-(trifluoromethyl)benzene	367-86-2	C₇H₃F₄NO₂	详情	详情
(XI)	39343	methyl 2-(5-chloro-2-methoxyphenyl)-2-[2-nitro-4-(trifluoromethyl)phenyl]acetate		C₁₇H₁₃ClF₃NO₅	详情	详情
(XII)	39344	methyl 2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]acetate		C₁₇H₁₂ClF₄NO₅	详情	详情
(XIII)	39345	2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]acetic acid		C₁₆H₁₀ClF₄NO₅	详情	详情
(XIV)	39346	(2S)-2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]ethanoic acid		C₁₆H₁₀ClF₄NO₅	详情	详情

Extended Information