4-Methylpyrimidine → 1-(4-Fluoro-phenyl)-2-pyrimidin-4-YL-ethanone

HRID 1374713Notes

Reaction equation

HRID 1374713 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][N:3]=1.[F:8][C:9]1[CH:19]=[CH:18][C:12]([C:13](OCC)=[O:14])=[CH:11][CH:10]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.O>[F:8][C:9]1[CH:19]=[CH:18][C:12]([C:13](=[O:14])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][N:3]=2)=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 189224-MethylpyrimidineHCID 67976Benzoic acid, 4-fluoro-, ethyl esterHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 117360541-(4-Fluoro-phenyl)-2-pyrimidin-4-YL-ethanoneYield 98.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-methylpyrimidine (20.64 g, 0.22 mol) and ethyl 4-fluorobenzoate (36.9 g, 0.22 mol) in dry THF (100 mL) at 0° C. under nitrogen was added lithium bis(trimethylsilyl)amide (1M in THF, 440 mL, 0.44 mol) over a 2 h period. A white precipitate deposited during the addition and this suspension was stirred at room temperature overnight. The reaction was diluted with 100 mL of water and filtered. The filtrate was washed with water (3×) and dried. The solution was diluted with ethyl acetate (100 mL) and the organic phase separated. The aqueous phase was further extracted with ethyl acetate (100 mL). Organic phases were dried (MgSO4) and concentrated and combined with the filtrate to give a combined yield of 47 g (98%) of product. 1H NMR (CDCl3) exists as a 2:1 mixture of enol:keto tautomers: 6 enol form: 5.95 (s, 1H), 6.92 (dd, J=1.2, 5.7 Hz, 1H), 7.06–7.14 (m, 2H), 7.83 (dd, J=5.4, 8.7 Hz, 2H), 8.40 (d, J=5.7 Hz, 1H), 8.8 (s, 1H); keto form: 4.42 (s, 2H), 7.12–7.18 (m, 2H), 7.34 (d, J=4.2 Hz, 1H), 8.06 (dd, J=5.3, 8.8 Hz, 2H), 8.67 (d, J=5.1 Hz, 1H), 9.16 (s, 1H); APESI-MS m/z 215 (M−1)−.

Workup

  1. additionA white precipitate deposited during the addition
  2. filtrationfiltered
  3. washThe filtrate was washed with water (3×)
  4. customdried
  5. additionThe solution was diluted with ethyl acetate (100 mL)
  6. customthe organic phase separated
  7. extractionThe aqueous phase was further extracted with ethyl acetate (100 mL)
  8. dry with materialOrganic phases were dried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-98867fccc0a04453acc25e17e7d08e58
Source dataset
uspto-grants-2007_01
Patent number
US07166597B2

Reaction notes

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