Methanol → (4R,5R)-5-(3-Fluorophenyl)-4-(2-methoxy-5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one

Reaction equation

F[C:2]1[C:7]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[O:11][C:10](=[O:20])[NH:9]2)=[CH:6][C:5]([C:21]#[C:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:4][N:3]=1.[OH-:29].[K+].[CH3:31]O>>[F:19][C:15]1[CH:14]=[C:13]([C@H:12]2[O:11][C:10](=[O:20])[NH:9][C@@H:8]2[C:7]2[C:2]([O:29][CH3:31])=[N:3][CH:4]=[C:5]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:6]=2)[CH:18]=[CH:17][CH:16]=1

Participants

Reactant 3

HCID 887Methanol2×

HCID 14797Potassium Hydroxide

HCID 69084163(4R,5R)-4-(2-Fluoro-5-(phenylethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

Product 1

HCID 69086137(4R,5R)-5-(3-Fluorophenyl)-4-(2-methoxy-5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one

Procedure

To a solution of (4R,5R)-4-(2-fluoro-5-(phenylethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (10 mg, 0.027 mmol) in methanol (0.25 mL) at 0° C. was added a solution of potassium hydroxide (14.9 mg, 0.266 mmol) in methanol (0.25 mL, 6.18 mmol). After 1 h at 0° C., the reaction was allowed to stir at room temperature for 24 h. The reaction was quenched by addition of solid ammonium chloride (30 mg) and concentrated. The resulting residue was dissolved in dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. The product was purified by Prep HPLC (TFA/MeOH, sunfire column) and concentrated to give 7.7 mg (73%). 1H NMR (CDCl3) δ: 8.38 (d, J=2.1 Hz, 1H), 7.84-7.88 (m, 1H), 7.53-7.58 (m, 2H), 7.43 (td, J=7.9, 5.8 Hz, 1H), 7.36-7.40 (m, 3H), 7.24 (dd, J=7.6, 0.6 Hz, 1H), 7.19 (dt, J=9.4, 2.0 Hz, 1H), 7.09-7.15 (m, 1H), 5.90 (s, 1H), 5.37 (d, J=4.3 Hz, 1H), 4.98 (d, J=4.3 Hz, 1H), 4.00 (s, 3H). 13C NMR (CDCl3) δ: 163.1, 160.1, 158.8, 150.1, 141.1, 137.8, 131.7, 130.7, 128.7, 128.6, 122.7, 121.4, 121.1, 121.1, 116.0, 114.1, 112.8, 91.8, 85.4, 83.1, 58.6, 54.1. Mass spec.: 389.2 (MH)+.