Sodium hydride → (4S,5S)-4-benzyl-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-methyl-1,3-oxazolidin-2-one
Reaction equation
C(O[C:6](=[O:19])[NH:7][C@@H:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C@H:9]([OH:11])[CH3:10])(C)(C)C.[H-].[Na+].Br[CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[C:37]([F:43])=[CH:36][C:35]=1[O:44][CH3:45]>>[CH2:12]([C@H:8]1[C@H:9]([CH3:10])[O:11][C:6](=[O:19])[N:7]1[CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([CH:40]([CH3:42])[CH3:41])[C:37]([F:43])=[CH:36][C:35]=1[O:44][CH3:45])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1Participants
Reactant 3
Product 1
Procedure
tert-butyl[(1S,2R)-1-benzyl-2-hydroxypropyl]carbamate (Step B, 39 mg, 0.148 mmol) was treated with sodium hydride (60% in oil, 12 mg, 0.309 mmol) and 2′-(bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl (Intermediate 10, 50 mg, 0.123 mmol) as described in Example 305 to afford (4S,5S)-4-benzyl-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-methyl-1,3-oxazolidin-2-one as a clear glass. LCMS=516.4 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.68 (d, J=11.5 Hz, 1H), 7.66-7.63 (m, 1H), 7.39-7.36 (m, 1H), 7.28-7.23 (m, 3H), 7.07 (d, J=8.5 Hz, 1H), 6.94 (d, J=6.9 Hz, 2H), 6.73 (d, J=4.8 Hz, 1H), 4.81 (d, J=16 Hz, 1H) 4.38 (d, J=16.1 Hz, 1H), 4.28-4.23 (m, 1H), 3.78 (s, 3H), 3.29-3.17 (m, 2H), 2.81 (dd, J=13.3, 3.9 Hz, 1H), 2.38-2.28 (m, 1H), 1.29-1.13 (m, 6H), 0.98 (d, J=6.2 Hz, 3H).
Sources & evidence
- ORD record
- ord-b52bd38295a948fc9f43242c1784c119
- Source dataset
- uspto-grants-2010_01
- Patent number
- US07652049B2
Reaction notes
Loading…