Sodium hydride → HCID 22663906, compound

HRID 392444Notes

Reaction equation

HRID 392444 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][CH:3]=1.[H-].[Na+].[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][C:26]=1F)[C:22]#[N:23]>CN(C=O)C>[F:18][C:19]1[CH:20]=[C:21]([C:22]#[N:23])[CH:24]=[CH:25][C:26]=1[O:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 506617HCID 506617, compoundHCID 5872033,4-Difluorobenzonitrile

Product 1

HCID 22663906HCID 22663906, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-(4-hydroxyphenyl)-3-pyridylmethylamine (1.0 equiv.) in DMF (0.1-0.3M) was treated with sodium hydride (1.0-1.5 equiv.)(60% dispersion in mineral oil). The reaction mixture was allowed to stir at room temperature for 30 minutes. The solution was then treated with 3,4-difluorobenzonitrile (1.6 equiv.) and allowed to stir. When complete (about 3 hours) the reaction mixture was partitioned between ethyl acetate/0.1M K2CO3, the organic layer separated, and the aqueous layer extracted 3 times with ethyl acetate. The organic layers were combined, washed with brine, and dried over MgSO4. The organic phase was concentrated in vacuo and purified by recrystallization from ethyl acetate/hexanes to give N-(4-(2-fluoro-4-cyanophenoxy)phenyl)-3-pyridylmethyl-amine 1H NMR(400 MHz, DMSO-d6): 4.29(2H, d, J=5.9 Hz), 6.40(1H, t, J=5.5 Hz), 6.63-6.65(2H, m), 6.83(1H, t, J=8.6 Hz), 6.90-6.92(2H, m), 7.33-7.36(1H, m), 7.55-7.57(1H, m), 7.74-7.76(1H, m), 7.93-7.97(1H, m), 8.43-8.44(1H, m), 8.58(1H, s). MS Found 320.1 [M+H]+.

Workup

  1. stirringto stir
  2. customWhen complete (about 3 hours) the reaction mixture was partitioned between ethyl acetate/0.1M K2CO3
  3. customthe organic layer separated
  4. extractionthe aqueous layer extracted 3 times with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. concentrationThe organic phase was concentrated in vacuo
  8. custompurified by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5a4cca2be93a46cca8517ed8aa735ef5
Source dataset
uspto-grants-2004_10
Patent number
US06800651B2

Reaction notes

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