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

Participants

Reaction Conditions

Reaction Steps

To a stirred, cold (0-5° C.) solution of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo-[1,2-b]pyrazole-2-carboxamide (300 g, 1.54 mol, in anhydrous tetrahydrofuran (3.0 L) under a nitrogen atmosphere is added slowly, in portions, lithium aluminum hydride (pellets, 30 g, 0.79 mol) over a period of 0.5 hours. After stirring for 5 hours at 0-5° C. the reaction is quenched by slowly adding saturated sodium sulfate solution (75 mL) to the stirred reaction mixture maintained at 5-15° C. Magnesium sulfate (70 g) is added and the mixture is stirred for 15 minutes. The mixture is then filtered and the filter pad is washed with tetrahydrofuran (1.0 L). The solvent is removed by evaporation at 20-70° C. under diminished pressure to provide a tan-colored oil. The oil is diluted with dichloromethane (1.0 L) and the solution is washed with 1.5 N hydrochloric acid (350 mL). The organic layer is separated and concentrated under aspirator vacuum at 20-70° C. to an oil. Fresh dichloromethane (1.00 L) and water (1.50 L) containing dissolved sodium hydrogensulfite (220 g) are added to the oil. The mixture is stirred for 15 minutes and the phases are separated. The aqueous phase is washed with dichloromethane (2×300 mL). Dichloromethane (1.0 L) and 10 N sodium hydroxide (220 mL) are added (with cooling) to the aqueous phase and the mixture is stirred for 10 minutes The lower organic phase is separated and washed with water (500 mL). The dichloromethane extract is evaporated under diminished pressure at 20-70° C. to give an oil, which crystallizes on cooling, to provide 140.1 g (67%) of 5,6-dihydro-4H-pyrrolo-[1,2-b]pyrazole-2-carbaldehyde, as a white, crystalline solid having, m.p 40-42° C., 1H NMR (300 MHz, CDCl3) 2.67-2.75 (m, 2H), 2.95 (t, 2H, J=7.3 Hz), 4.22 (t, 2H, J=7.3 Hz), 6.52 (s, 1H), 9.89 (s, 1H) and HPLC-MS purity, 99.86% at 12.9 minutes:

Provenance & Evidence