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

Participants

Reaction Steps

To a slurry of (R)-2-(1-aminoethyl)-1-tosyl-1H-pyrrole-3-carboxylic acid compound with 2,2,2-trifluoroacetic acid (1:1) (702d; 22.83 g, 54.1 mmol) in 150 mL EtOAc at 0° C. was added DIPEA (28.2 mL, 162 mmol). A portion of the slurry seemed to dissolve. After 10 min, 1-propanephosphonic acid cyclic anhydride (T3P) (50 wt. % solution in EtOAc; Matrix Scientific; 35.0 mL, 59.5 mmol) was added and much of the solid dissolved. After 10 min, the still heterogeneous reaction was warmed to RT. After 4 h, the reaction was dark brown and homogeneous. The reaction was treated with 400 mL sat'd aq. NaHCO3 and transferred to a separatory funnel. The layers were separated and the organic layer was washed with 1× sat'd aq. NaHCO3 then 1× brine, dried over anhydrous Na2SO4, filtered through a glass frit and concentrated in vacuo to give (R)-6-methyl-1-tosyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one (16.5 g, 56.8 mmol, quantitative yield) as a tan foam. 1H NMR (400 MHz, CDCl3) δ ppm 7.70-7.77 (2H, m), 7.35 (2H, d, J=8.0 Hz), 7.16 (1H, d, J=3.3 Hz), 6.48 (1H, d, J=3.1 Hz), 5.75 (1H, br. s.), 4.68 (1H, q, J=6.5 Hz), 1.62 (3H, d, J=6.7 Hz). m/z (ESI, +ve) 291.0 (M+H)+.

Provenance & Evidence