Ethanol → HCID 46191617, compound

HRID 541121Notes

Reaction equation

HRID 541121 reaction equation
C(O)C.[BH4-].[Na+].[F:6][C:7]1[CH:19]=[C:18]([C:20]2[CH:21]=[N:22][N:23]([CH:25]([CH:31]=[O:32])[C:26](OCC)=[O:27])[CH:24]=2)[C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([OH:37])([C:33]([F:36])([F:35])[F:34])[C:9]=2[CH:8]=1>O1CCCC1>[F:6][C:7]1[CH:19]=[C:18]([C:20]2[CH:21]=[N:22][N:23]([CH:25]([CH2:31][OH:32])[CH2:26][OH:27])[CH:24]=2)[C:17]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([OH:37])([C:33]([F:36])([F:35])[F:34])[C:9]=2[CH:8]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 4311764Sodium borohydrideHCID 59492510HCID 59492510, compound

Product 1

HCID 46191617HCID 46191617, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of ethanol (80 ml) and sodium borohydride (16.2 g), a solution of an optically active form (13.2 g) of ethyl 2-[4-(2-fluoro-9-hydroxy-9-trifluoromethyl-9H-fluoren-4-yl)-pyrazol-1-yl]-3-oxo-propionate in tetrahydrofuran (80 ml) was added dropwise over 25 min. At this time, the temperature of the reaction mixture was controlled with an ice-bath not to exceed 30° C. The ice-bath was changed to a water-bath, and the mixture was stirred for 17 hr. Then, the water-bath was removed and the mixture was further stirred for 4 hr. The reaction mixture was ice-cooled, 2N hydrochloric acid was added and the mixture was stirred. To this mixture were added ethyl acetate and water, and the mixture was partitioned in a separatory funnel. The aqueous layer was further extracted with ethyl acetate, and the extract was combined with the organic layer obtained earlier. The organic layer was successively washed with water and saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1 to 15/1) to give the title compound (7.38 g, 84%).

Workup

  1. customAt this time, the temperature of the reaction mixture was controlled with an ice-bath
  2. customto exceed 30° C
  3. customThen, the water-bath was removed
  4. stirringthe mixture was further stirred for 4 hr
  5. temperaturecooled
  6. addition2N hydrochloric acid was added
  7. stirringthe mixture was stirred
  8. additionTo this mixture were added ethyl acetate and water
  9. customthe mixture was partitioned in a separatory funnel
  10. extractionThe aqueous layer was further extracted with ethyl acetate
  11. customobtained earlier
  12. washThe organic layer was successively washed with water and saturated brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customthe obtained residue was purified by silica gel column chromatography (eluent: chloroform/methanol=30/1 to 15/1)

Sources & evidence

ORD record
ord-541be3d4fa504550884a4a186c830bc9
Source dataset
uspto-grants-2014_10
Patent number
US08871934B2

Reaction notes

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