Sodium Methoxide → Razuprotafib sodium

Participants

Reaction Conditions

Reaction Steps

trimethyl-ammonium (4-((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)-phenyl)sulfamate (70) was added to a stirred reactor containing methanol (MeOH) (4.87 vol.) and sodium methoxide (25% solution in MeOH) (0.093 eq.). Sodium methoxide (25% solution in MeOH) (1.08 eq.) was added over 5 minutes while maintaining the temperature at 19 to 25° C. The resulting mixture was stirred at 19-25° C. for 30 to 60 minutes then 2 portions of sodium methoxide (25% solution in MeOH) (0.14 eq. and 0.07 eq.) are added over 30 minutes while maintaining the temperature at 19 to 25° C. The resulting mixture was stirred for 30 to 60 minutes while maintaining the temperature at 19 to 25° C. The reaction mixture was then filtered and the filter cake washed with methanol (MeOH). The filtrates and cake washes are concentrated under reduced pressure at 30 to 40° C. to approximately 8 volumes. The reaction mixture was cooled to 19 to 25° C. and methyl t-butyl ether (10 vol) was then added. The reaction mixture was then stirred for 15 to 20 minutes. The resulting solids are isolated by filtration and the filter cake was washed with MTBE. The wet cake was dried under vacuum at room temperature or 35-40° C. for a minimum of 2 hours to afford the desired product.

Provenance & Evidence