Methanol → (4-tert-Butylphenyl)[(4S)-5-(4-fluorophenyl)-4-hydroxy-7-isopropyl-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl]methanone

HRID 1516734Notes

Reaction equation

HRID 1516734 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[C:12]([C:16]1[CH:46]=[CH:45][C:19]([C:20]([C:22]2[C:23]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)=[C:24]3[C:29](=[CH:30][C:31]=2[CH:32]([CH3:34])[CH3:33])[O:28][C:27]([CH3:36])([CH3:35])[CH2:26][C:25]3=[O:37])=[O:21])=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13].CO>O1CCCC1>[C:12]([C:16]1[CH:17]=[CH:18][C:19]([C:20]([C:22]2[C:23]([C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)=[C:24]3[C:29](=[CH:30][C:31]=2[CH:32]([CH3:34])[CH3:33])[O:28][C:27]([CH3:35])([CH3:36])[CH2:26][C@@H:25]3[OH:37])=[O:21])=[CH:45][CH:46]=1)([CH3:14])([CH3:15])[CH3:13]

Participants

5

Reactant 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 580030386-(4-tert-butylbenzoyl)-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one

Product 1

HCID 58003042(4-tert-Butylphenyl)[(4S)-5-(4-fluorophenyl)-4-hydroxy-7-isopropyl-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl]methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

78 μl (540 μmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 2.46 mg (20 μmol) of (1R,2S)-1-aminoindan-2-ol in 2 ml of tetrahydrofuran. The mixture is then cooled to 0° C., and a solution of 52 mg (110 μmol) of 6-(4-tert-butylbenzoyl)-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 29A) in 3 ml of tetrahydrofuran are slowly added dropwise. The mixture is then allowed to thaw slowly and stirred at room temperature 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 preparative HPLC (method 1) and subsequent chiral HPLC (method 2) gives the target compound.

Workup

  1. customthe solvent is removed under reduced pressure
  2. washwashed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification of the residue by preparative HPLC (method 1) and subsequent chiral HPLC (method 2)
  6. customgives the target compound

Sources & evidence

ORD record
ord-e24588c71f084ee6ac1f9d22fde12556
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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