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【结 构 式】

【分子编号】28293

【品名】methyl 4-(difluoromethoxy)benzoate

【CA登记号】

【 分 子 式 】C9H8F2O3

【 分 子 量 】202.1575264

【元素组成】C 53.47% H 3.99% F 18.8% O 23.74%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

Reaction of methyl 4-hydroxybenzoate (XI) with difluorochloromethane and potassium tert-butoxide provided difluoromethyl ether (XII). After basic hydrolysis of the methyl ester of (XII), the resulting carboxylic acid (XIII) was converted to acid chloride (XIV) by means of refluxing SOCl2. Subsequent coupling of (XIV) with benzyl bromide in the presence of Zn and palladium catalyst produced the diaryl ethanone (XV). Reductive amination of (XV) with ammonium formate at 160 C gave formamide (XVI), which was hydrolyzed to racemic amine (XVII) with boiling HCl. Alkylation of this amine with the intermediate iodide (X) in THF at 110 C in a sealed flask yielded a diastereomeric mixture of secondary amines (XVIII), which were separated by column chromatography. The required (R,R)-isomer was desilylated employing tetrabutylammonium fluoride and AcOH to produce aminoalcohol (XIX). Finally, hydrogenolytic cleavage of the benzyl ether of (XIX) furnished the title compound.

1 Washburn, W.N.; Girotra, R.N.; Sher, P.M.; Mikkilineni, A.B.; Poss, K.M.; Mathur, A.; Gavai, A.; Bisacchi, G.S. (Bristol-Myers Squibb Co.); Catecholamine surrogates useful as B3 agonists. CA 2138675; EP 0659737; JP 1995206806; US 5776983 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 20636 N-(2-(benzyloxy)-5-[(1R)-2-iodo-1-[(triethylsilyl)oxy]ethyl]phenyl)methanesulfonamide C22H32INO4SSi 详情 详情
(XI) 10251 methyl 4-hydroxybenzoate; Methyl p-hydroxybenzoate 99-76-3 C8H8O3 详情 详情
(XII) 28293 methyl 4-(difluoromethoxy)benzoate C9H8F2O3 详情 详情
(XIII) 28294 4-(difluoromethoxy)benzoic acid 4837-20-1 C8H6F2O3 详情 详情
(XIV) 28295 4-(difluoromethoxy)benzoyl chloride C8H5ClF2O2 详情 详情
(XV) 28296 1-[4-(difluoromethoxy)phenyl]-2-phenyl-1-ethanone C15H12F2O2 详情 详情
(XVI) 28297 1-[4-(difluoromethoxy)phenyl]-2-phenylethylformamide C16H15F2NO2 详情 详情
(XVII) 28298 1-[4-(difluoromethoxy)phenyl]-2-phenyl-1-ethanamine C15H15F2NO 详情 详情
(XVIII) 28299 N-(2-(benzyloxy)-5-[(1R)-2-([1-[4-(difluoromethoxy)phenyl]-2-phenylethyl]amino)-1-[(triethylsilyl)oxy]ethyl]phenyl)methanesulfonamide C37H46F2N2O5SSi 详情 详情
(XIX) 28300 N-[2-(benzyloxy)-5-[(1R)-2-([(1R)-1-[4-(difluoromethoxy)phenyl]-2-phenylethyl]amino)-1-hydroxyethyl]phenyl]methanesulfonamide C31H32F2N2O5S 详情 详情
Extended Information