Dichloromethane → Cevidoplenib

Participants

Reaction Steps

To a slurry of intermediate 2 (500 mg, 1.14 mmol), (S)-isoxazolidin-4-ol hydrochloride (220 mg, Tetrahedron Lett., 2006, 47, 7635-7639) and triethylamine (0.79 mL) in 10 mL of dichloromethane and 10 mL of N,N-dimethylacetamide (DMAC), was added NaBH(OAc)3 (730 mg, 3.42 mmol) at room temperature. Volatiles were removed in vacuo. It was extracted with dichloromethane (×3). The collected organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to give 270 mg (50%) of the desired compound 1 as a pale yellow solid; MS (ESI) m/z 474 [M+H]+, 1H NMR (300 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.30 (s, 1H), 9.02 (s, 1H), 8.48 (d, J=5.4 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.13 (d, J=5.4 Hz, 1H), 5.19 (s, 1H), 4.60 (d, 1H), 4.10 (m, 1H), 3.94 (d, 2H), 3.87 (s, 3H), 3.81 (m, 1H), 2.86 (m, 1H), 2.65 (m, 1H), 2.29 (s, 1H), 0.92 (d, J=6.0 Hz, 2H).

Provenance & Evidence