Thionyl Chloride → 7-(4-Chloro-3-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

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Reaction Steps

To an ice-water bath cooled solution of 4-(4-chloro-3-fluoro-phenoxy)-2-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester (2.529 g) in THF (20 mL) was added a solution of potassium tert-pentoxide (4.5 mL, 1.7 M in toluene); the mixture was stirred at rt for 60 min after addition; then the mixture was quenched with 2 M HCl, diluted with EtOAc and water, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulphate, filtered off, concentrated to give the desired cyclized intermediate. This intermediate was then dissolved in DCM (30 mL) and treated with thionyl chloride (0.63 mL) overnight. Then concentrated, the residue was dissolved in EtOAc, washed with water, diluted NaCl solution, then dried over sodium sulphate, filtered, concentrated and the residue was column purified to give the desired product (580 mg). LC MS ESI: 362 (M+1)+.

Provenance & Evidence