Chloroacetyl chloride → HCID 66665363, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (R)-2-amino-2-(5-bromo-2-fluoro-phenyl)-3,3-difluoro-propan-1-ol HCl salt (0.5 g, 1.56 mmol) in IPAc (5 ml) was added under argon a solution of K2CO3 (0.862 g, 6.24 mmol) in 5 ml water below 25° C. After stirring for 30 min at 25° C. to provide a diphase clear solution, cooled down to −5° C., a solution of 2-chloroacetyl chloride (0.41 g, 3.59 mmol) in IPAc (2 mL) was added slowly with the temperature below 10° C. After stirring for 30 min at 20° C., the organic phase was collected and used for next step directly. THF (3 ml) was added to the above solution, the mixture was cooled to 0° C. The solution was added under argon KOtBu (0.35 g, 3.12 mmol) below 10° C. After stirring at 20° C. for 3 h, water was added to quench the reaction. The organic phase was washed by 1N HCl water solution (5 ml). The organic phase was collected and used for next step directly. The above solution was added water (5 ml) and Pd/C (10%, 50 mg), the mixture was stirred under H2 (1.5 bar) at 25° C. for 3 h. The catalyst was filtered out. The filtration was washed by 15% NaCl water solution. The solvent was removed under vacuum to provide the title compound as yellowish solid. ESIMS: 246 [(M+H)+]. 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 7.57 (m, 1H), 7.48 (m, 1H), 7.30 (m, 1H), 7.81 (m, 1H), 7.30 (m, 2H), 6.55 (t, 1H), 4.1 (m, 4H).

Provenance & Evidence