Methanol → (4S)-5-Cyclopentyl-7-isopropyl-2,2-dimethyl-6-[4-(trifluoromethyl)benzyl]chroman-4-ol

HRID 1516741Notes

Reaction equation

HRID 1516741 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[CH:12]1([C:17]2[C:26]([CH2:27][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:38]([CH3:40])[CH3:39])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:43])[CH2:20][C:21]([CH3:42])([CH3:41])[O:22]3)[CH2:16][CH2:15][CH2:14][CH2:13]1.CO>O1CCCC1>[CH:12]1([C:17]2[C:26]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([C:34]([F:35])([F:36])[F:37])=[CH:32][CH:33]=3)=[C:25]([CH:38]([CH3:39])[CH3:40])[CH:24]=[C:23]3[C:18]=2[C@@H:19]([OH:43])[CH2:20][C:21]([CH3:41])([CH3:42])[O:22]3)[CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 580030055-Cyclopentyl-7-isopropyl-2,2-dimethyl-6-[4-(trifluoromethyl)benzyl]-2,3-dihydro-4H-chromen-4-one

Product 1

HCID 58003007(4S)-5-Cyclopentyl-7-isopropyl-2,2-dimethyl-6-[4-(trifluoromethyl)benzyl]chroman-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

40 μl (210 μmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 1.2 mg (10 μmol) of (1R,2S)-1-aminoindan-2-ol in 1.5 ml of tetrahydrofuran, and the mixture is stirred for 30 min. A solution of 23 mg (50 μmol) of 5-cyclopentyl-7-isopropyl-2,2-dimethyl-6-[4-(trifluoromethyl)benzyl]-2,3-dihydro-4H-chromen-4-one (Example 39A) in 1.5 ml of tetrahydrofuran is then added very slowly 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 residue by preparative HPLC (method 1) gives the target product.

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 residue by preparative HPLC (method 1)
  7. customgives the target product

Sources & evidence

ORD record
ord-3954e28ba17e4dd7b36ac391aae48e11
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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