Phosphorus oxychloride → 3-chloro-1-(4-fluorophenyl)pyrazin-2(1H)-one

HRID 1676399Notes

Reaction equation

HRID 1676399 reaction equation
O=P(Cl)(Cl)[Cl:3].[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:18]=[CH:17][N:16]=[C:15](OC)[C:14]2=[O:21])=[CH:9][CH:8]=1>CN(C=O)C>[Cl:3][C:15]1[C:14](=[O:21])[N:13]([C:10]2[CH:11]=[CH:12][C:7]([F:6])=[CH:8][CH:9]=2)[CH:18]=[CH:17][N:16]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 224243451-(4-fluorophenyl)-3-methoxypyrazin-2(1H)-one

Product 1

HCID 672214163-chloro-1-(4-fluorophenyl)pyrazin-2(1H)-oneYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

POCl3 (5.6 mL, 61.3 mmol) was added dropwise to a solution of 1-(4-fluorophenyl)-3-methoxypyrazin-2(1H)-one in DMF (30 mL) with stirring at 0° C. followed by heating at 90° C. for 1.5 hours. The residue was cooled to 0° C., quenched by adding saturated sodium acetate solution, extracted with CH2Cl2, washed with water, dried over MgSO4, and concentrated. The crude was purified by silica gel flash column chromatography (0.7% MeOH in CH2Cl2) to afford 3.52 g (64%) of the desired product. LRMS (ESI pos) m/e 224.9, 227.0 (M+1, Cl pattern). 1H-NMR (400 MHz, CDCl3) δ 7.41 (m, 2H), 7.21 (m, 4H); 19F-NMR (376 MHz, CDCl3) δ −110.9.

Workup

  1. temperatureby heating at 90° C. for 1.5 hours
  2. temperatureThe residue was cooled to 0° C.
  3. customquenched
  4. additionby adding saturated sodium acetate solution
  5. extractionextracted with CH2Cl2
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe crude was purified by silica gel flash column chromatography (0.7% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a0a78b5b22e747f38dafdae4484df8da
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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