Dimethylformamide → N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a cooled (5-6° C.), stirred suspension of crude potassium 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxylate (21.9 g, 115 mmol) in dichloromethane (180 mL) containing N,N-dimethylformamide (2.5 mL, 32.3 mmol), is added, dropwise, oxalyl chloride (19.0 mL, 218 mmol) over a period of 10 minutes. The reaction is exothermic with gas evolution. After the addition, the ice-bath is removed and the reaction mixture stirred at room temperature. After 5 hours, the solution is added to a cooled, stirred (10-12° C.) suspension of N,O-dimethylhydroxylamine hydrochloride (17.6 g, 180 mmol) in dichloromethane (80 mL) containing N,N-diisopropylethyamine (100 mL, 574 mmol). After 18 hours at room temperature, water (150 mL) is added. The two layers are separated. The organic layer is extracted with water (3×150 mL), and the organic layer dried over anhydrous sodium sulfate, filtered and concentrated under diminished pressure to give a brown solid which is recrystallized from ether (35 mL) to give 15.6 g (69%) of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]-pyrazole-2-carboxamide as a brown solid having HPLC purity, 91.3% (HPLC conditions described in Example 17).

Provenance & Evidence