Diisopropylamine → HCID 19883412, compound

Participants

Reaction Conditions

Reaction Steps

A cooled (-60° C.) solution of diisopropylamine (11.13 g, 0.110 mole) in anhydrous tetrahydrofuran (150 ml) under nitrogen was treated (via syringe) with 2.4N n-butyllithium/hexane (0.105 mole), warmed to -20° C., stirred for 5 minutes, then treated in portions with 4-(N-acetylamino)-5-chloro-2-methoxybenzoic acid, methyl ester (25.8 g, 0.100 mole). After 30 minutes at 25° C., the mixture was cooled (0° C.), treated dropwise with a solution of methanesulfonyl chloride (25.0 g, 0.218 mole) in anhydrous tetrahydrofuran (50 ml), and maintained at room temperature for 30 minutes and at 50° C. for one hour. The mixture was partially concentrated in vacuo and added to ice water (600 ml), and the aqueous mixture was extracted with methylene chloride (3×250 ml). The combined organic solution was dried (sodium sulfate), concentrated in vacuo, taken up in 60:40 water/ethanol (300 ml), treated with potassium hydroxide (33.6 g, 0.60 mole), and refluxed for three hours. Most of the ethanol was removed in vacuo and replaced with water, and the aqueous solution was extracted with ether (2×200 ml), then cooled in an ice bath and treated with concentrated hydrochloric acid solution (60 ml). The suspension was filtered and the solid was washed with water, air dried, and recrystallized from 95% ethanol to afford 14.60 g (52%) of the title compound as a colorless solid; mp 248°-250° C.

Provenance & Evidence