Sodium hydride → HCID 53709065, compound

HRID 2396860Notes

Reaction equation

HRID 2396860 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:15][CH3:16])=[C:5](C(O)=O)[NH:6]2.[H-].[Na+].[CH3:19][C@@H:20]1[CH2:22][O:21]1>C1(OC2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:15][CH3:16])=[CH:5][N:6]2[CH2:19][C@H:20]([OH:21])[CH3:22]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 146261(R)-1,2-EpoxypropaneHCID 18986296HCID 18986296, compound

Product 1

HCID 53709065HCID 53709065, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 7583Diphenyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1.2 g of 4-chloro-5-fluoro-3-ethyl-indole-2-carboxylic acid in 16 ml of diphenyl ether was stirred at 260° for 4 hours and, after cooling to 0°, diluted with 24 ml of tetrahydrofuran. 186 mg of sodium hydride dispersion were added and the mixture was stirred for one hour. Subsequently, 0.5 ml of (R)-methyloxirane was added and the reaction mixture was stirred at room temperature for 114 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 (1:2) and subsequently with toluene-ethyl acetate (9:!). 102 g (80%) of (R)-1-(4-chloro-5-fluoro-3-ethylindol-1-yl)-propan-2-ol were obtained as pale brown crystals with m.p. 87°-88°.

Workup

  1. temperatureafter cooling to 0°
  2. stirringthe mixture was stirred for one hour
  3. stirringthe reaction mixture was stirred at room temperature for 114 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 (1:2) and subsequently with toluene-ethyl acetate (9:!)

Sources & evidence

ORD record
ord-58cfc25ce7ab420b92e950b4fb663216
Source dataset
uspto-grants-1996_02
Patent number
US05494928

Reaction notes

Loading…