Diisobutylaluminumhydride → [(4S)-4-{[tert-Butyl(dimethyl)silyl]oxy}-7-cyclopentyl-5-(4-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanol

HRID 1516690Notes

Reaction equation

HRID 1516690 reaction equation
[Si:1]([O:8][C@@H:9]1[C:18]2[C:13](=[CH:14][C:15]([CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)=[C:16]([C:26]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[O:27])[C:17]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[O:12][C:11]([CH3:44])([CH3:43])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.[Na].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[Si:1]([O:8][C@@H:9]1[C:18]2[C:13](=[CH:14][C:15]([CH:38]3[CH2:39][CH2:40][CH2:41][CH2:42]3)=[C:16]([CH:26]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=3)[OH:27])[C:17]=2[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[O:12][C:11]([CH3:44])([CH3:43])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 21225700Diisobutylaluminumhydride2×HCID 58002981HCID 58002981, compoundHCID 86594854CID 86594854

Product 1

HCID 58002967[(4S)-4-{[tert-Butyl(dimethyl)silyl]oxy}-7-cyclopentyl-5-(4-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

Under argon, 102 mg (0.16 mmol) of [(4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-cyclopentyl-5-(4-fluorophenyl)-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl][4-(trifluoromethyl)phenyl]methanone (Example 13A) are initially charged in 2 ml of abs. toluene and cooled to −78° C. 250 μl (0.25 mmol) of a diisobutylaluminum hydride solution (1 M in hexane) are slowly added dropwise, and the mixture is stirred at −78° C. After 30 min, another 80 μl (0.08 mmol) of diisobutylaluminum hydride solution (1 M in hexane) are added dropwise, and the mixture is stirred for another 30 min. 20% strength sodium/potassium tartrate solution is added, and the mixture is extracted repeatedly with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product obtained is purified by preparative thick-layer chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 5:1). This gives 47 mg (46% of theory) of the title compound which is used in the next step without further characterization.

Workup

  1. stirringthe mixture is stirred for another 30 min
  2. extractionthe mixture is extracted repeatedly with ethyl acetate
  3. washThe combined organic phases are washed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-33e37f8e8da845479155eb2d73b3be89
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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