Sodium hydride → HCID 90387231, compound

Participants

Reaction Steps

To a solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (1.56 g, 8.3 mmol) in THF (20 mL) was added NaH (0.33 g, 8.3 mmol) under nitrogen at 0° C. The mixture was warmed to RT over a 30 minute period and 1,3-dichloro-7-fluoroisoquinoline (0.9 g, 4.17 mmol) was added. The resulting mixture was stirred for 10 hours at RT. The mixture was subsequently diluted with EtOAc (100 mL), quenched with saturated aqueous NH4Cl (100 mL), and extracted with EtOAc (3×100 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by column chromatography eluting with petroleum ether and ethyl acetate (PE/EtOAc=50:1-10:1 gradient) to give the title compound (1.1 g, 72%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.00-7.98 (m, 1H), 7.82-7.80 (m, 2H), 7.62 (s, 1H), 5.67-5.63 (d, J=16 Hz, 1H), 3.69-3.66 (m, 1H), 3.53-3.487 (m, 3H), 2.30-2.22 (m, 2H), 1.41-1.39 (d, J=10.8 Hz, 2H).

Provenance & Evidence