Toluene → (4S)-7-cyclopentyl-5-(4-fluorophenyl)-6-{(R)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-2,2-dimethylchroman-4-ol

HRID 1516726Notes

Reaction equation

HRID 1516726 reaction equation
[CH:1]1([C:6]2[CH:15]=[C:14]3[C:9]([C@@H:10]([OH:18])[CH2:11][C:12]([CH3:17])([CH3:16])[O:13]3)=[C:8]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:7]=2[C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[O:27])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC=CC=1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>O>[CH:1]1([C:6]2[CH:15]=[C:14]3[C:9]([C@@H:10]([OH:18])[CH2:11][C:12]([CH3:16])([CH3:17])[O:13]3)=[C:8]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:7]=2[C@H:26]([OH:27])[C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:32][CH:33]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 9855836Potassium sodium tartarateHCID 21225700Diisobutylaluminumhydride2×HCID 25022900[(4S)-7-Cyclopentyl-5-(4-fluorophenyl)-4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanone

Product 1

HCID 58002939(4S)-7-cyclopentyl-5-(4-fluorophenyl)-6-{(R)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-2,2-dimethylchroman-4-ol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Under argon, 120 mg (0.23 mmol) of [(4S)-7-cyclopentyl-5-(4-fluorophenyl)-4-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanone (Example 12A) are initially charged in 2 ml of abs. toluene and cooled to −78° C. At this temperature, 0.59 ml (0.59 mmol) of diisobutylaluminum hydride solution (1 M in toluene) is slowly added dropwise, and stirring of the mixture is then continued at −78° C. for 2 h. Diisobutylaluminum hydride is then added in such an amount that no more starting material can be detected. Saturated potassium sodium tartrate solution is then added, and the mixture is diluted with water and extracted with ethyl acetate. The combined organic phases are washed once with saturated sodium chloride solution. The organic phase is dried over sodium sulfate, filtered and concentrated. The residue is purified by thick-layer chromatography (mobile phase: cyclohexane/ethyl acetate 5:1), resulting in the separation of the diastereomers.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic phases are washed once with saturated sodium chloride solution
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue is purified by thick-layer chromatography (mobile phase: cyclohexane/ethyl acetate 5:1)
  7. customresulting in the separation of the diastereomers

Sources & evidence

ORD record
ord-10e9e7af6609422bbc51554b2a1959de
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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