Potassium Carbonate → (R)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one

Participants

Reaction Steps

To a stirring solution of (R)-6-methyl-1-tosyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (702e; 15.6 g, 53.7 mmol) in 250 mL MeOH under nitrogen in an ice/water bath was added K2CO3 (14.85 g, 107 mmol). The slurry was stirred and the bath was allowed to slowly expire overnight. The stir bar was removed; 100 g silica gel was added; and the reaction was concentrated in vacuo. A DCM-wetted pad of silica gel (4 cm) was poured in a 15 cm diameter flitted funnel and the dried silica gel/reaction mixture was placed on the silica gel pad and covered with 4 cm sand. 1 L fractions collected: #1—1 L DCM; #2—1 L 10% MeOH/DCM; #3—1 L 10% MeOH/DCM; #4—750 mL 10% MeOH/DCM #5—1 L 10% MeOH/DCM. Fractions 3-5 were combined and concentrated in vacuo to give 7.7 g (74% ee) as a tan solid. The material was further purified by chiral SFC (mobile phase CO2/15% MeOH (20 mM NH3), chiral column ASH (250×30 mm), wave length 256 nm, flow rate 120 mL/min). The second eluting peak was collected and concentrated in vacuo to give (R)-6-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (702) (5.3 g, 39.0 mmol, 73% yield) as an off-white solid. 1H NMR (400 MHz, MeOH-d4) δ ppm 6.84 (1H, d, J=2.9 Hz), 6.23 (1H, d, J=2.9 Hz), 4.53 (1H, q, J=6.7 Hz), 1.41 (3H, d, J=6.8 Hz). m/z (ESI, +ve) 137.1 (M+H)+.

Provenance & Evidence