Sodium Bicarbonate → 7-(3,4-Dichlorophenyl)-6-(hydroxymethyl)-1,4-oxazepan-6-ol monohydrochloride

Participants

Reaction Conditions

Reaction Steps

Bismuth(III)trifluoromethanesulfonate (228 mg) was added to a mixed solution of tert-butyl (3RS,4SR)-4-(3,4-dichlorophenyl)-1,5-dioxa-8-azaspiro[2.6]nonane-8-carboxylate (59 mg) in THF/water (v/v=4/1, 5 mL), and the mixture was stirred at 80° C. overnight. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 4 mL) of hydrogen chloride in ethyl acetate. The solvent was evaporated under reduced pressure. To a solution of the residue in THF (4 mL) were added triethylamine (0.033 mL) and di-tert-butyl dicarbonate (52 mg), and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate, and the mixture was stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure, 8 M aqueous sodium hydroxide solution (3 mL) was added, and the mixture was stirred at 90° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To the residue was added a solution (4 M, 3 mL) of hydrogen chloride in ethyl acetate. The solvent was evaporated under reduced pressure to give the title compound (7 mg).

Provenance & Evidence