Propyl p-toluenesulfonate → (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine p-TSA

Participants

Reaction Steps

A 72 liter unjacketed reactor was charged with 1.84 kg (10.87 mol) of (6R)-2,6 diamino-4,5,6,7-tetrahydro-benzothiazole ((6R) diamine), followed by 14.7 L of dimethyl formamide (DMF). Under continuous stirring, the mixture was heated to a temperature of between 65° C. and 68° C. A solution of 2926 grams propyl tosylate and 1761 grams diisopropylethyleamine in 3.5 L DMF was added slowly over a period of 2 hours. The reaction was continued at 67° C. for an additional 4 hours, after which the solution was gradually cooled to room temperature (18° C. to 22° C.) and stirred for an additional 15 hours. The solution was diluted with 14.7 L of MTBE over a time period of 30 minutes, and stirred for an additional 1 hour. The precipitated material was collected by filtration and washed with 7.3 L MTBE, followed by 3 washes of 3.7 L each of ethanol, and a wash with 9.2 L heptane. The washed precipitated cake was dried under high vacuum at 30° C. to 35° C. The final weight of the dried product was 2090-grams, representing a 50% yield.

Provenance & Evidence