Hydrochloric Acid → HCID 86728107, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(2-(5-bromo-2-fluorophenyl)-1-((2-cyanopropan-2-yl)sulfonyl)-3-fluoropropan-2-yl)-2-methylpropane-2-sulfinamide (45 g, 93 mmol) in dioxane (800 mL) was added hydrochloric acid, 4.0M solution in 1,4-dioxane (107 mL, 428 mmol). The reaction mixture was heated to 100° C. for 2 d. The reaction was allowed to cool to RT, concentrated, and dried under high vacuum to give a light brown solid. The solids were triturated in DCM, filtered, rinsed, and dried to give a white solid. The compound was separated into its enantiomers via prep-scale supercritical fluid chromatography using a Chiralpak AD-H column with an isocratic 75% carbon dioxide/25% methanol with 0.2% ammonia solvent system to yield (R)-5-amino-3-(5-bromo-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (41.4 g, 109 mmol, 78% yield) and (S)-5-amino-3-(5-bromo-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (38.6 g, 101 mmol, 73%) LC/MS (ESI+) m/z=380.9; 382.9 for both diastereomers. (M+H; 2 bromine isotopes).

Provenance & Evidence