Sodium hydride → (6S)-3-{[2'-chloro-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methoxyphenyl)-1,3-oxazinan-2-one

HRID 537994Notes

Reaction equation

HRID 537994 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C@H:9]1[O:14][C:13](=[O:15])[NH:12][CH2:11][CH2:10]1.C(OC(=O)CCC(C1C=CC=CC=1OC)=O)C.CC1C=C([C@H]2OC(=O)NCC2)C=C(C)C=1.[H-].[Na+].Br[CH2:51][C:52]1[CH:57]=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:55]=[CH:54][C:53]=1[C:62]1[CH:67]=[C:66]([CH:68]([CH3:70])[CH3:69])[CH:65]=[CH:64][C:63]=1[Cl:71]>>[Cl:71][C:63]1[CH:64]=[CH:65][C:66]([CH:68]([CH3:69])[CH3:70])=[CH:67][C:62]=1[C:53]1[CH:54]=[CH:55][C:56]([C:58]([F:59])([F:60])[F:61])=[CH:57][C:52]=1[CH2:51][N:12]1[CH2:11][CH2:10][C@@H:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[O:14][C:13]1=[O:15]

Participants

6

Reactant 5

HCID 24758Sodium hydrideHCID 13495321Ethyl 4-(2-methoxyphenyl)-4-oxobutyrateHCID 575443622-(Bromomethyl)-2'-chloro-5'-isopropyl-4-(trifluoromethyl)biphenyl2×HCID 57544374(6S)-6-(3,5-dimethylphenyl)-1,3-oxazinan-2-oneHCID 68997782(6S)-6-(2-methoxyphenyl) 1,3-oxazinan-2-one

Product 1

HCID 24739764(6S)-3-{[2'-chloro-5'-isopropyl-4-(trifluoromethyl)biphenyl-2-yl]methyl}-6-(2-methoxyphenyl)-1,3-oxazinan-2-one

Procedure

(6S)-6-(2-methoxyphenyl) 1,3-oxazinan-2-one (prepared from ethyl-4-(2-methoxyphenyl)-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; 39 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-methoxyphenyl)-1,3-oxazinan-2-one as a white solid. LCMS=518.1 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.76 (s, 1H), 7.64 (d, J=8.1 Hz, 1H), 7.50 (d, J=6.4 Hz, 1H), 7.44 (s, 1H), 7.37-7.35 (m, 1H), 7.34-30 (m, 1H), 7.26-7.24 (m, 1H), 7.09 (dd, J=7.8, 2.3 Hz, 1H), 7.06-7-7.00 (m, 1H), 6.90 (d, J=8.2 Hz, 1H), 5.66 (dd, J=8.7, 3.0 Hz, 1H), 4.71 (d, J=15.8 Hz, 1H), 4.39 (d, J=15.8 Hz, 1H), 3.85 (s, 3H), 3.25-3.17 (m, 1H), 3.09-3.04 (m, 1H), 2.97-2.92 (m, 1H), 2.31-2.25 (m, 1H), 2.06-1.99 (m, 1H) 1.28 (d, J=7.1 Hz, 6H).

Sources & evidence

ORD record
ord-bf35f866e3a6493d8c74decc136b8644
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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