Methanol → (4s)-5-Cyclopent-1-yl-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethylchroman-4-ol

HRID 1516740Notes

Reaction equation

HRID 1516740 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[CH:12]1([C:17]2[C:26]([CH:27]([OH:38])[C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:41])[CH3:40])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:44])[CH2:20][C:21]([CH3:43])([CH3:42])[O:22]3)[CH2:16][CH2:15][CH2:14][CH2:13]1.CO>O1CCCC1>[CH:12]1([C:17]2[C:26]([C@H:27]([OH:38])[C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:40])[CH3:41])[CH:24]=[C:23]3[C:18]=2[C@@H:19]([OH:44])[CH2:20][C:21]([CH3:42])([CH3:43])[O:22]3)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 58002966Rac-5-cyclopent-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Product 1

HCID 58002963(4s)-5-Cyclopent-1-yl-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethylchroman-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

23 μl (130 μmol) of borane/N,N-diethylaniline complex are added to a solution of 0.1 mg (6.7 μmol) of (1R,2S)-1-aminoindan-2-ol in 1.0 ml of tetrahydrofuran, and the mixture is stirred for 30 min. A solution of 15 mg (33 μmol) of 5-cyclopent-1-yl-6-{hydroxy[4-(trifluormethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 38A) in 1.0 ml of tetrahydrofuran is then added dropwise, and the mixture is stirred for 2 h. Methanol is then added, and the mixture is concentrated 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 crude product by preparative HPLC (method 1) gives the diastereomerically pure target compounds.

Workup

  1. stirringthe mixture is stirred for 2 h
  2. concentrationthe mixture is concentrated 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 crude product by preparative HPLC (method 1)
  7. customgives the diastereomerically pure target compounds

Sources & evidence

ORD record
ord-033c8cb829ea4ea3a6d02b1be5592176
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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