Sodium hydride → HCID 53763671, compound

HRID 2396845Notes

Reaction equation

HRID 2396845 reaction equation
[F:1][C:2]1[C:3]([C:14]([F:17])([F:16])[F:15])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](C(O)=O)=[CH:5]2.[H-].[Na+].[CH3:20][C@H:21]1[CH2:23][O:22]1>C1(OC2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[F:1][C:2]1[C:3]([C:14]([F:15])([F:16])[F:17])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:20][C@H:21]([OH:22])[CH3:23])[CH:6]=[CH:5]2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 146262(2S)-2-MethyloxiraneHCID 18986211HCID 18986211, compound

Product 1

HCID 53763671HCID 53763671, compoundYield 35.5%

Reagents, catalysts & solvents 2

HCID 7583Diphenyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 0.8 g of 5-fluoro-4-trifluoromethylindole-2-carboxylic acid in 16 ml of diphenyl ether was stirred at 260° for 4 hours and, after cooling to 0°, diluted with 16 ml of tetrahydrofuran. 122 mg of sodium hydride dispersion were added and the mixture was stirred for 1 hour. Subsequently, 0.46 ml of (S)-methyloxirane was added and the reaction mixture was stirred at room temperature for 60 hours. The mixture was extracted with diethyl ether, water and saturated sodium chloride solution and the organic phase was dried over sodium sulfate. The solvent was removed and the residue was chromatographed over 40 g of silica gel with hexane-toluene (1:1) and subsequently with toluene-ethyl acetate (15:1). There was obtained 0.3 g (35.5%) of (R)-1-(5-fluoro-4-trifluoromethyl-indol-1-yl)-propan-2-ol as light brown crystals.

Workup

  1. temperatureafter cooling to 0°
  2. stirringthe mixture was stirred for 1 hour
  3. stirringthe reaction mixture was stirred at room temperature for 60 hours
  4. extractionThe mixture was extracted with diethyl ether, water and saturated sodium chloride solution
  5. dry with materialthe organic phase was dried over sodium sulfate
  6. customThe solvent was removed
  7. customthe residue was chromatographed over 40 g of silica gel with hexane-toluene (1:1) and subsequently with toluene-ethyl acetate (15:1)

Sources & evidence

ORD record
ord-d6d4ee46f7b2403f92b0e0b063c62e93
Source dataset
uspto-grants-1996_02
Patent number
US05494928

Reaction notes

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