Ethanol → (+)-2-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-2-methyl-propane-1,3-diol

HRID 541158Notes

Reaction equation

HRID 541158 reaction equation
[F:1][C:2]1[CH:14]=[C:13]([C:15]2[CH:16]=[N:17][N:18]([C:20]([CH3:26])([CH2:24][OH:25])[C:21](O)=[O:22])[CH:19]=2)[C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:4]=2[CH:3]=1.C(O)C.O.C(=O)([O-])O.[Na+]>O1CCCC1>[F:1][C:2]1[CH:14]=[C:13]([C:15]2[CH:16]=[N:17][N:18]([C:20]([CH3:26])([CH2:21][OH:22])[CH2:24][OH:25])[CH:19]=2)[C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 516892Sodium BicarbonateHCID 594927112-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-3-hydroxy-2-methyl-propionic acid

Product 1

HCID 46191679(+)-2-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-2-methyl-propane-1,3-diolYield 67.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of an optically active form (26.6 g) of 2-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-3-hydroxy-2-methyl-propionic acid in tetrahydrofuran (40 ml) was added dropwise at room temperature a 1.09M solution (200 ml) of borane-tetrahydrofuran complex in tetrahydrofuran, and the mixture was stirred for 3 hr. To the reaction mixture was added dropwise ethanol (25 ml) at room temperature and the mixture was stirred at 80° C. for 1 hr. To this mixture were added water (200 ml) and saturated aqueous sodium hydrogen carbonate (100 ml) and the mixture was extracted twice with ethyl acetate (100 ml). The combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform/methanol=20/1 to 10/1) to give the title compound (17.4 g).

Workup

  1. stirringthe mixture was stirred at 80° C. for 1 hr
  2. extractionthe mixture was extracted twice with ethyl acetate (100 ml)
  3. washThe combined organic layer was successively washed twice with water (100 ml) and once with saturated brine (100 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform/methanol=20/1 to 10/1)

Sources & evidence

ORD record
ord-3774942b38e546abb2694f4b192338a1
Source dataset
uspto-grants-2014_10
Patent number
US08871934B2

Reaction notes

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