Sodium Hydroxide → HCID 178482601, compound

Participants

Reaction Steps

A mixture of trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-amino}-cyclohexyl)-3H-benzoxazol-2-one (51) (190 mg, 0.464 mmol) from Step 7, p-formaldehyde (70 mg, 2.32 mmol), and 2N NaOH (1 mL) in MeOH (15 mL) was stirred for 3 hours, NaBH(OAc)3 (138 mg, 0.650 mmol) was added, and the reaction mixture was stirred overnight. Solid NaOH was added until the solution turned clear. The reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (silica gel, 95:5:1 CH2Cl2:MeOH:NH4OH) gave trans-6-(4-{[3-(4-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-methyl-amino}-cyclohexyl)-3H-benzoxazol-2-one (52) (60 mg, 31%), as a white foam: mp 109-114° C.; IR (KBr): 3430, 2927, 1772 cm−1; 1H NMR (500 MHz, DMSO-d6) δ 7.74 (dd, J=6, 3 Hz, 2H), 7.27 (m, 2H), 7.13 (s, 1H), 6.97 (m, 2H), 4.55 (m, 1H), 3.33 (m, 2H), 3.18 (m, 2H), 2.56 (m, 1H), 2.44 (m, 1H), 2.28 (s, 3H), 1.87 (m, 4H), 1.38 (m, 2H), 1.26 (m, 2H); API-MS (m/z): 424 [M+H]+; HRMS-API (m/z): [M+H]+ calcd for C24H26FN3O3, 424.2036; found, 424.2036; HPLC: method A, 5.39 minutes (98.1%); method B, 10.86 minutes (>99%).

Provenance & Evidence