Methyl iodide → HCID 178471798, compound

Reaction equation

[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[NH:31][C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].I[CH3:52]>C1COCC1>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[N:31]([CH3:52])[C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:4]=[C:3]([C:2]([F:1])([F:47])[F:48])[CH:8]=1

Participants

Procedure

A stirred solution of ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}carbonyl)cyclohexyl]acetate (500 mg; 0.716 mmol) in anhydrous THF (10 mL) was cooled to 0° C. and treated with sodium hydride (60% in oil; 31.5 mg; 0.788 mmol). The resultant mixture was stirred at 0° C. for 30 min prior to addition of iodomethane (58 μL; 0.931 mmol). The reaction was stirred at room temperature for 14 h and quenched with H2O. The reaction was partitioned between EtOAc (50 mL) and H2O (50 mL) and the aqueous layer was extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with EtOAc/hexanes, and by chiral HPLC (chiralPak IA column, 10% iPrOH/heptane) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](methyl)amino]carbonyl}cyclohexyl)acetate as a clear oil. LCMS=713.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.92 (s, 1 H), 7.80 (s, 1 H), 7.73 (s, 1H), 7.29-7.20 (m, 2 H), 7.17-7.15 (m, 1 H), 5.66 (d, J=8.3 Hz, 1 H), 4.95 (d, J=14.8 Hz, 1 H), 4.22 (d, J=16.7 Hz, 1 H), 4.14-4.06 (m, 2 H), 3.897 (d, J=14.7 Hz, 1 H), 3.39 (s, 3 H), 2.70-2.63 (m, 1 H), 2.22-2.18 (m, 1 H), 2.10-2.07 (m, 1 H), 2.00-1.52 (m, 8 H), 1.27-1.19 (m, 3 H), 1.16-1.08 (m, 1 H), 0.76-0.68 (m, 3 H).