Water → (1S,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-({[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)propan-1-ol

HRID 1028538Notes

Reaction equation

HRID 1028538 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([C@@H:13]2[O:17]C(=O)[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[CH:32][C:31]=3[O:39][CH3:40])[C@H:14]2[CH3:41])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[K+].CCOC(C)=O>CCO>[F:1][C:2]([F:42])([F:43])[C:3]1[CH:4]=[C:5]([C@H:13]([OH:17])[C@@H:14]([NH:15][CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:23]=[CH:22][C:21]=2[C:30]2[CH:35]=[C:34]([CH:36]([CH3:37])[CH3:38])[CH:33]=[CH:32][C:31]=2[O:39][CH3:40])[CH3:41])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 53363913(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86603413(1S,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-({[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)propan-1-ol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (147.7 mg, 0.239 mmol) in EtOH (7.5 mL) was added H2O (1.5 mL) and KOH (150 mg, 2.67 mmol). The solution was heated to 75° C. for 30 h and then cooled to room temperature. EtOAc (75 mL) was added and the organic layer was washed with H2O (15 mL) and brine (2×15 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography to afford (1S,2S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)propan-1-ol. Rf=0.44 (40% EtOAc/hexanes). LCMS=594.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 6.93-7.78 (m, 9H), 3.51-4.20 (m, 6H), 2.91 (m, 1H), 2.49 (m, 1H), 1.22-1.26 (m, 6H), 0.79-0.81 (m, 3H).

Workup

  1. temperaturecooled to room temperature
  2. washthe organic layer was washed with H2O (15 mL) and brine (2×15 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-56884199dc7b4d3094ef617b514419e4
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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