Benzonitrile → HCID 66924316, compound

HRID 2176965Notes

Reaction equation

HRID 2176965 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH2:7][CH:6]([CH2:10][OH:11])[CH2:5]1.[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[C:17](F)[C:14]=1[C:15]#[N:16].C(#N)C1C=CC=CC=1>CN(C=O)C.O>[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[C:17]([O:11][CH2:10][CH:6]2[CH2:7][CH2:8][CH2:9][N:4]([CH3:3])[CH2:5]2)[C:14]=1[C:15]#[N:16]

Participants

7

Reactant 4

HCID 7505BenzonitrileHCID 24758Sodium hydride2×HCID 746952,6-DifluorobenzonitrileHCID 97998(1-Methyl-3-piperidyl)methanol

Product 1

HCID 66924316HCID 66924316, compoundYield 4.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60%; 316 mg; 7.9 mmol) was suspended in DMF and cooled to 0° C. 1-Methylpiperidin-3-ylmethanol (998 mg; 7.5 mmol) was added dropwise to the sodium hydride mixture. The solution was allowed to warm to room temperature and stirred for 30 minutes. The solution was then cooled to 0° C. 2,6-Difluorobenzonitrile (1.1 g; 7.9 mmol) in DMF was cooled to 0° C. and the alcohol mixture was added dropwise to the benzonitrile solution and allowed to warm to room temperature overnight. The solution was poured into water and extracted with dichloromethane and solvent removed. Purification by column chromatography (10% ethyl acetate/hexane) to yield 79 milligrams of 2-fluoro-6-(1-methylpiperidin-3-ylmethoxy)benzonitrile.

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe solution was then cooled to 0° C
  3. temperatureto warm to room temperature overnight
  4. extractionextracted with dichloromethane and solvent
  5. customremoved
  6. customPurification by column chromatography (10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-616ab713dd754c698002d50d669c63c3
Source dataset
uspto-grants-2015_06
Patent number
US09067897B2

Reaction notes

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