Methanol → HCID 58002995, compound

HRID 1516729Notes

Reaction equation

HRID 1516729 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]([C@@H:29]([F: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]([F: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 69071062HCID 69071062, compound

Product 1

HCID 58002995HCID 58002995, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

110 μl (630 μmol) of borane/N,N-diethylaniline complex are added slowly to a solution of 3.5 mg (20 μmol) of (1R,2S)-1-aminoindan-2-ol in 4 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 30 min. A solution of 77 mg (160 μmol) of 5-(4-fluorophenyl)-6-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 22A) in 4 ml of tetrahydrofuran are then slowly added dropwise, and the mixture is stirred at room temperature for 6.5 h. 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: cyclohexane/ethyl acetate 20:1) gives the diasteromerically pure target compounds.

Workup

  1. stirringthe mixture is stirred at room temperature for 6.5 h
  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: cyclohexane/ethyl acetate 20:1)
  7. customgives the diasteromerically pure target compounds

Sources & evidence

ORD record
ord-2b81908bedb1451eba15f7c77294707b
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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