Methanol → Ketorolac

Participants

Reaction Steps

A mixture of 34.4 g (100 mmol) 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide, 25 g sodium hydroxide in 25 mL water, and 80 mL methanol was refluxed for 5 hours. The mixture was cooled to room temperature, stirred under nitrogen for sixteen hours, and then diluted with 80 mL of water. The mixture was extracted with toluene (2×50 mL), and the aqueous and organic phases were separated. The aqueous phase was acidified with 6 N hydrochloric acid (110 mL). The resulting precipitate was extracted several times with dichloromethane (1×150 mL), (1×75 mL), (1×50 mL). The combined extract was treated with FILTROL® (activated clay decolorizing agent) (4.5 g) for 30 minutes, filtered, and concentrated by atmospheric distillation. Hexane (190 mL) was added and the entire mixture allowed to cool to room temperature and then further cooled to 0° C. to −5° C. The product, 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid (ketorolac) was collected by filtration, washed with 100 mL of hexane/dichloromethane (7:3 v/v), and dried at 60° C. to 70° C. under vacuum, to yield ketorolac (21.3 g, 83.4% yield), mp 152° C. to 162° C.

Provenance & Evidence