P-Cresol → 4-(p-Tolyloxy)pyrimidine-5-carbonitrile

HRID 1749402Notes

Reaction equation

HRID 1749402 reaction equation
[CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([CH3:8])[CH:2]=1.[H-].[Na+].Cl[C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[CH:14][N:13]=1>CS(C)=O>[C:3]1([CH3:8])[CH:4]=[CH:5][C:6]([O:7][C:12]2[C:17]([C:18]#[N:19])=[CH:16][N:15]=[CH:14][N:13]=2)=[CH:1][CH:2]=1

Participants

5

Reactant 3

HCID 2879P-CresolHCID 24758Sodium hydrideHCID 131269094-Chloropyrimidine-5-carbonitrile

Product 1

HCID 1181621664-(p-Tolyloxy)pyrimidine-5-carbonitrileYield 41.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

p-Cresol (1.0 equiv.) was placed in a round bottom flask with DMSO (1.0 M) and sodium hydride (0.9 equiv). The reaction mixture was stirred at ambient temperature for 5 min. To the mixture was added 4-chloropyrimidine-5-carbonitrile (1.0 equiv.). The reaction was stirred at 25° C. for 2 h. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine (3×) and dried over sodium sulfate. Volatile organic solvents were removed under reduced pressure to give 4-(p-tolyloxy)pyrimidine-5-carbonitrile (41.6% yield) as a light brown solid which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.24 (s, 1H), 8.94 (s, 1H), 7.29 (dd, J=0.8, 8.6 Hz, 2H), 7.21-7.16 (m, 2H), 2.34 (s, 3H). MS (ESI) m/z 211.7 [M+1]+.

Workup

  1. stirringThe reaction was stirred at 25° C. for 2 h
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine (3×)
  4. dry with materialdried over sodium sulfate
  5. customVolatile organic solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-bf6fcf3a1a494eda8de52152c43dbafa
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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