Methanol → (4s)-5-(4-Fluorophenyl)-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

HRID 1516728Notes

Reaction equation

HRID 1516728 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:28]([CH:29]([OH:40])[C:30]3[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=3)=[C:27]([CH:41]([CH3:43])[CH3:42])[CH:26]=[C:25]3[C:20]=2[C:21](=[O:46])[CH2:22][C:23]([CH3:45])([CH3:44])[O:24]3)=[CH:15][CH:14]=1.CO>O1CCCC1>[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:28]([C@H:29]([OH:40])[C:30]3[CH:35]=[CH:34][C:33]([C:36]([F:38])([F:39])[F:37])=[CH:32][CH:31]=3)=[C:27]([CH:41]([CH3:42])[CH3:43])[CH:26]=[C:25]3[C:20]=2[C@@H:21]([OH:46])[CH2:22][C:23]([CH3:44])([CH3:45])[O:24]3)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 69070570Rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Product 1

HCID 58002998(4s)-5-(4-Fluorophenyl)-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

340 μl (1.89 mmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 10.58 mg (70 μmol) of (1R,2S)-1-aminoindan-2-ol in ±1 ml of tetrahydrofuran, and the mixture is stirred for another 30 min. A solution of 230 mg (0.47 mmol) of rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 21A) in 11 ml of tetrahydrofuran are then very slowly added dropwise, and the mixture is stirred overnight. Methanol is then added, and the solvent is removed under reduced pressure. The residue is taken up in ethyl acetate and washed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution. The organic phase is dried over sodium sulfate and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (mobile phase: gradient cyclohexane/dichloromethane/ethyl acetate 40:40:1→2:2:1) gives the diastereomerically pure target compounds.

Workup

  1. stirringthe mixture is stirred overnight
  2. customthe solvent is removed under reduced pressure
  3. washwashed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by column chromatography on silica gel (mobile phase: gradient cyclohexane/dichloromethane/ethyl acetate 40:40:1→2:2:1)
  7. customgives the diastereomerically pure target compounds

Sources & evidence

ORD record
ord-d19559164da942fd8da9591fd689198e
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

Loading…