Sodium hydride → (6S)-3-{[2'-chloro-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methylphenyl)-1,3-oxazinan-2-one
Reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@H:8]1[O:13][C:12](=[O:14])[NH:11][CH2:10][CH2:9]1.C(OC(=O)CCC(C1C=CC=CC=1C)=O)C.CC1C=C([C@H]2OC(=O)NCC2)C=C(C)C=1.[H-].[Na+].Br[CH2:49][C:50]1[CH:55]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:53]=[CH:52][C:51]=1[C:60]1[CH:65]=[C:64]([CH:66]([CH3:68])[CH3:67])[CH:63]=[CH:62][C:61]=1[Cl:69]>>[Cl:69][C:61]1[CH:62]=[CH:63][C:64]([CH:66]([CH3:67])[CH3:68])=[CH:65][C:60]=1[C:51]1[CH:52]=[CH:53][C:54]([C:56]([F:57])([F:58])[F:59])=[CH:55][C:50]=1[CH2:49][N:11]1[CH2:10][CH2:9][C@@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[O:13][C:12]1=[O:14]Participants
Reactant 5
Product 1
Procedure
(6S)-6-(2-methylphenyl)-1,3-oxazinan-2-one (prepared from ethyl-4-(2-methylphenyl)-4-oxobutyrate by a procedure analogous to that reported for Intermediate 21; 20 mg; 0.10 mmol) was treated with sodium hydride (60% in oil; 8.0 mg; 0.20 mmol) and 2-(bromomethyl)-2′-chloro-5′-isopropyl-4-(trifluoromethyl)biphenyl (Intermediate 27; 41 mg; 0.10 mmol) as described in Example 11 to afford (6S)-3-{[2′-chloro-5′-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methylphenyl)-1,3-oxazinan-2-one as a white solid. LCMS=502.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.78 (s, 1H), 7.67-7.64 (m, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.45 (s, 1H), 7.40-7.37 (m, 1H), 7.28-7.24 (m, 3H), 7.19-7.17 (m, 1H), 7.11 (dd, J=8, 2.1 Hz, 1H), 5.51 (dd, J=9.9, 2.8 Hz, 1H), 4.69 (d, J=15.8 Hz, 1H), 4.45 (d, J=15.8 Hz, 1H), 3.31-3.21 (m, 1H), 3.14-3.10 (m, 1H), 2.98-2.93 (m, 1H), 2.35 (s, 3H), 2.20-2.15 (m, 1H), 2.14-2.04 (m, 1H) 1.29 (d, J=6.9 Hz, 6H).
Sources & evidence
- ORD record
- ord-22e6fa5148f24f79808e173e10349aeb
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08865707B2
Reaction notes
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