Methanol → (4S)-5-cyclohex-1-en-1-yl-6-{(R)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

HRID 1516739Notes

Reaction equation

HRID 1516739 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[C:12]1([C:18]2[C:27]([CH:28]([OH:39])[C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)=[C:26]([CH:40]([CH3:42])[CH3:41])[CH:25]=[C:24]3[C:19]=2[C:20](=[O:45])[CH2:21][C:22]([CH3:44])([CH3:43])[O:23]3)[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]=1.CO>O1CCCC1>[C:12]1([C:18]2[C:27]([C@H:28]([OH:39])[C:29]3[CH:30]=[CH:31][C:32]([C:35]([F:37])([F:38])[F:36])=[CH:33][CH:34]=3)=[C:26]([CH:40]([CH3:41])[CH3:42])[CH:25]=[C:24]3[C:19]=2[C@@H:20]([OH:45])[CH2:21][C:22]([CH3:43])([CH3:44])[O:23]3)[CH2:17][CH2:16][CH2:15][CH2:14][CH:13]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 580029855-Cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one

Product 1

HCID 58003012(4S)-5-cyclohex-1-en-1-yl-6-{(R)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-di-methylchroman-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

230 μl (1.27 mmol) of borane/N,N-diethylaniline complex are added very slowly to a solution of 7.10 mg (50 μmol) of (1R,2S)-1-aminoindan-2-ol in 7.5 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 30 min. A solution of 150 mg (320 μmol) of 5-cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 35A) in 7.5 ml of tetrahydrofuran are then added very slowly dropwise over a period of 30 min. 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→cyclohexane/ethyl acetate 20:1→10:1→1:1) and subsequent preparative HPLC (method 1) gives the diastereomerically pure target compounds, which for their part are present as a mixture of two rotamers.

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→cyclohexane/ethyl acetate 20:1→10:1→1:1) and subsequent preparative HPLC (method 1)
  7. customgives the diastereomerically pure target compounds, which for their part
  8. additionare present as a mixture of two rotamers

Sources & evidence

ORD record
ord-dd4f7aab29824d3db478f244ec70d462
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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