Sodium hydride → HCID 53685914, compound

HRID 2396856Notes

Reaction equation

HRID 2396856 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[NH:5][C:4]=1C(O)=O)[CH3:2].[H-].[Na+].[CH3:18][C@@H:19]1[CH2:21][O:20]1>C1(OC2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[CH2:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]([CH2:18][C@H:19]([OH:20])[CH3:21])[CH:4]=1)[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 146261(R)-1,2-EpoxypropaneHCID 3159594HCID 3159594, compound

Product 1

HCID 53685914HCID 53685914, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 7583Diphenyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1.21 g of 3-ethyl-5-fluoroindole-2-carboxylic acid in 16 ml of diphenyl ether was stirred at 260° for 2 hours and, after cooling to 0°, diluted with 29 ml of tetrahydrofuran. 218 mg of sodium hydride dispersion were added and the mixture was stirred for one hour. Subsequently, 0.61 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 sulfate. The solvent was removed and the residue was chromatographed over 120 g of silica gel with hexane-toluene (1:2) and subsequently with toluene-ethyl acetate (9:1). 0.8 g (62%) of (R)-1-(3-ethyl-5-fluoro-indol-1-yl)-propan-2-ol was obtained as pale brown crystals with m.p. 65°-67°.

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 sulfate
  6. customThe solvent was removed
  7. customthe residue was chromatographed over 120 g of silica gel with hexane-toluene (1:2) and subsequently with toluene-ethyl acetate (9:1)

Sources & evidence

ORD record
ord-5de8c0e98359465981ee62f179cf952f
Source dataset
uspto-grants-1996_02
Patent number
US05494928

Reaction notes

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