Trifluoroacetic acid → 5-Benzyl-2-methyl-tetrahydro-pyrrolo[3,4-c]pyrrole-1,3-dione

Temperature

0 °C

N-Methylmaleimide (23.3 g, 21 mmol; Aldrich) was dissolved in CH2Cl2 (400 mL) in a 3-neck flask, chilled to 0° C. under nitrogen, and treated with trifluoroacetic acid (1.6 mL, 21 mmol; Aldrich). A solution of N-(methoxymethyl)-N-(trimethylsilylmethyl)-benzylamine (49.8 g, 21 mmol; Aldrich) in CH2Cl2 (60 mL) was then added slowly at a rate to maintain the temperature below about 5° C. After the addition was complete, the ice bath was removed and the reaction mixture was stirred for 24 h. The solution was concentrated under vacuum, and the residue was diluted with CH2Cl2 (125 mL), washed with saturated aqueous NaHCO3 (2×100 mL) and brine (2×100 mL). The organic phase was concentrated under vacuum to afford the title compound as a white solid (51.2 g, 21 mmol; 100% yield): 1H NMR (300 MHz, CDCl3) δ ppm 7.14-7.37 (m, 5H), 3.57 (s, 2H), 3.28 (d, J=10.2 Hz, 2H), 3.13-3.21 (m, 2H), 3.01 (s, 3H), 2.32-2.42 (m, 2H); MS (DCl/NH3) m/z 245 (M+H)+.

1. temperatureto maintain the temperature below about 5° C
2. additionAfter the addition
3. customthe ice bath was removed
4. concentrationThe solution was concentrated under vacuum
5. additionthe residue was diluted with CH2Cl2 (125 mL)
6. washwashed with saturated aqueous NaHCO3 (2×100 mL) and brine (2×100 mL)
7. concentrationThe organic phase was concentrated under vacuum

ORD record

ord-b00bade11201466d88f1c462e9294ca1

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07365193B2