Dichloroacetyl chloride → 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(3-(methylsulfonamidomethyl)isoxazol-5-yl)phenyl)propan-2-yl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a dimethylformamide (3 ml) solution of (1R,2S)-3-fluoro-1-hydroxy-1-(4-(3-(methylsulfonamidomethyl)isoxazol-5-yl)phenyl)propan-2-aminium chloride (150 mg, 0.40 mmol) is added diisopropylethylamine (0.255 g, 2 mmol). After cooling the reaction mixture to 0° C. dichloroacetyl chloride (62 mg, 0.42 mmol) is added. The reaction is stirred at 0° C. for twenty minutes then quenched by the addition of water (1 ml). The reaction mixture is concentrated to a volume of approximately two milliliters and subjected to reverse phase HPLC purification to give the title compound (95 mg): 1H NMR (400 MHz, CDCl3) 3.06 (s, 3 H) 4.30-4.43 (m, 1 H) 4.49 (d, J=6.32 Hz, 2 H) 4.56-4.67 (m, 2 H) 4.93 (m, br, 1 H) 5.19-5.24 (m, 1 H) 5.87 (s, 1 H) 6.61 (s, 1 H) 7.03 (d, J=9.09 Hz, 1 H) 7.52 (d, J=8.08 Hz, 2 H) 7.79 (d, J=8.59 Hz, 2 H); m/z (Cl) 454, 456, 458 ([M+H]+.

Provenance & Evidence