(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropenylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one

HRID 537989Notes

Reaction equation

HRID 537989 reaction equation
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[C:26]([C:27]4[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=4[O:37][CH3:38])=[CH:25][CH:24]=[C:23]([C:39]([CH3:41])=[CH2:40])[N:22]=3)[C@@H:15]([CH3:42])[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H][H]>CCO.[Pd]>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[C:26]([C:27]4[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=4[O:37][CH3:38])=[CH:25][CH:24]=[C:23]([CH:39]([CH3:41])[CH3:40])[N:22]=3)[C@@H:15]([CH3:42])[CH2:14]2)[CH:4]=[C:3]([C:2]([F:1])([F:43])[F:44])[CH:8]=1

Participants

5

Reactant 2

HCID 24739434(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropenylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 24739597(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A solution of (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropenylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one (Example 5, 8.0 mg, 0.011 mmol) in EtOH (2 mL) was charged with hydrogen at 1 atm with catalytic amount of Pd/C. The mixture was stirred at room temperature for 1 h. The mixture was filtered through Celite and concentrated. The title compound was obtained after flash chromatography on silica gel using EtOAc:hexane 10:90 as the elute to afford 4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-6-isopropylpyridin-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one. LCMS=627.2 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.86 (s, 3H), 7.68 (brs, 1H), 7.18 (brs, 1H), 7.14 (br m, 1H), 6.71 (d, J=11.9 Hz, 1H), 5.31-5.27 (m, 2H), 4.31-4.24 (m, 2H), 3.80 (s, 3H), 2.21 (m, 1H), 1.82 (m, 1H), 1.26 (br s, 3H), 1.21 (br m, 12H).

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-ab979ef5374e4986b95cd8831124e738
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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