N-methyl-2-pyrrolidone → HCID 90387132, compound

Participants

Reaction Conditions

Reaction Steps

To a 25 mL microwave vial was added N-methyl-2-pyrrolidinone (10.00 mL) and tert-butyl trans-3-hydroxy-4-methylpyrrolidine-1-carboxylate (1.118 g, 5.55 mmol). The mixture was cooled to 0° C. under a nitrogen atmosphere. To this mixture was added portion-wise NaH (60% suspension in mineral oil, 0.202 g, 5.05 mmol). After 5 minutes the mixture was allowed to warm to RT and was stirred for 10 minutes. Next, 1,3-dichloroisoquinoline (1 g, 5.05 mmol) was added and the reaction mixture was heated in a microwave reactor at 135° C. for 30 minutes. The reaction mixture was subsequently diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated onto silica. The crude product was purified by flash column chromatography (SiO2) eluting with a gradient of 5-50% heptane in EtOAc to give the title compound as a white solid (1.066 g, 58.2%). 1H NMR (500 MHz, CDCl3) δ ppm 1.16 (d, 3H), 1.48 (s, 9H), 2.60 (br s, 1H), 3.23 (br s, 1H), 3.49 (br s, 1H), 3.74 (br s, 1H), 3.94 (br s, 1H), 5.38 (br s, 1H), 7.23-7.32 (m, 1H), 7.51 (ddd, 1H), 7.61-7.71 (m, 2H), 8.17 (d, 1H); ESI-MS m/z [M+H]+ 307.6.

Provenance & Evidence