Sodium hydride → HCID 53945475, compound

HRID 2396861Notes

Reaction equation

HRID 2396861 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](C(O)=O)=[C:5]2[CH3:14].[H-].[Na+].[CH3:17][C@@H:18]1[CH2:20][O:19]1>C1(OC2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:17][C@H:18]([OH:19])[CH3:20])[CH:6]=[C:5]2[CH3:14]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 146261(R)-1,2-EpoxypropaneHCID 11329675-Fluoro-3-methyl-1H-indole-2-carboxylic acid

Product 1

HCID 53945475HCID 53945475, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 7583Diphenyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1.16 g of 5-fluoro-3-methyl-indole-2-carboxylic acid in 16 ml of diphenyl ether was stirred at 260° for 5 hours and, after cooling to 0°, diluted with 30 ml of tetrahydrofuran. 225 mg of sodium hydride dispersion were added and the mixture was stirred for one hour. Subsequently, 0.63 ml of (R)-methyloxirane was added and the reaction mixture was stirred at room temperature for 90 hours. The mixture was extracted with diethyl ether, water and saturated sodium chloride solution and the organic phase was dried over sodium surfate. The solvent was removed and the residue was chromatographed over 120 g of silica gel with hexane-toluene (1:1) and subsequently with toluene-ethyl acetate (19:1). 0.87 g (70%) of (R)-1-(5-fluoro-3-methylindol-1-yl)-propan-2-ol was obtained as a pale brown oil.

Workup

  1. temperatureafter cooling to 0°
  2. stirringthe mixture was stirred for one hour
  3. stirringthe reaction mixture was stirred at room temperature for 90 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 surfate
  6. customThe solvent was removed
  7. customthe residue was chromatographed over 120 g of silica gel with hexane-toluene (1:1) and subsequently with toluene-ethyl acetate (19:1)

Sources & evidence

ORD record
ord-016a5262032b43d0ab7f5ad734611c42
Source dataset
uspto-grants-1996_02
Patent number
US05494928

Reaction notes

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