Sodium hydride → (S)-tert-butyl 3-((7-chloro-3-cyanoisoquinolin-1-yl)oxy)pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (201 mg, 1.076 mmol) in THF (5 mL) at 0° C. was added NaH (81 mg, 1.35 mmol). The reaction mixture was stirred at RT for 30 minutes. Next, 1,7-dichloroisoquinoline-3-carbonitrile (200 mg, 0.897 mmol) was added and the reaction mixture was warmed to RT over a 1 hour period. The reaction was quenched with saturated aqueous NH4Cl (10 mL) and the resulting mixture was extracted with EtOAc (3×50 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and concentrated. The crude product was purified by preparative TLC eluting with petroleum ether and ethyl acetate (PE/EtOAc=3:1) to give the title compound (200 mg, 59%). 1H NMR (400 MHz, CDCl3) δ ppm 8.15 (s, 1H), 7.65-7.71 (m, 3H), 5.74 (br, 1H), 3.46-3.69 (m, 4H), 2.23 (s, 1H), 1.49 (s, 9H).

Provenance & Evidence