Sodium hydride → HCID 66924128, compound

HRID 1364428Notes

Reaction equation

HRID 1364428 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18](F)[C:15]=1[C:16]#[N:17]>CN(C)C=O.O>[F:13][C:14]1[CH:21]=[CH:20][C:19]([O:10][C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH3:9])=[CH:18][C:15]=1[C:16]#[N:17]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 746952,6-DifluorobenzonitrileHCID 6950742(R)-1-(3-Chlorophenyl)ethanol

Product 1

HCID 66924128HCID 66924128, compoundYield 50.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of (R)-1-(3-chlorophenyl)ethanol (0.730 g, 4.66 mmol) in dimethylformamide (5 mL) was added to a 0° C. slurry of sodium hydride (0.207 g, 5.18 mmol) in dimethylformamide (5 mL) under nitrogen atmosphere. The reaction mixture was warmed to room temperature, stirred for 3 hour, and then cooled with an ice bath. The cold orange solution was added dropwise to a 0° C. solution of 2,6-difluorobenzonitrile (0.720 g, 5.18 mmol) in dimethylfomamide (5 mL). After the reaction was stirred at ambient temperature for around 18 hours, the reaction was diluted with water and extracted with EA. The organic layer was washed with water and brine, dried over MgSO4, and concentrated in vacuo to a yellow semi-solid. Flash chromatography purification (silica gel, 50% hexane in DCM) afforded the 2-fluoro-5-[(R)-1-(3-chlorophenyl)ethoxy]benzonitrile as a pale yellow oil (0.645 g, 50%).

Workup

  1. temperaturecooled with an ice bath
  2. stirringAfter the reaction was stirred at ambient temperature for around 18 hours
  3. extractionextracted with EA
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo to a yellow semi-solid
  7. customFlash chromatography purification (silica gel, 50% hexane in DCM)

Sources & evidence

ORD record
ord-28e83a4fd577441a856cacf2618692d9
Source dataset
uspto-grants-2011_02
Patent number
US07888366B2

Reaction notes

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