Phosphorus oxychloride → Methyl 4-(3-chloro-1,2,4-triazin-6-yl)benzoate

HRID 1257873Notes

Reaction equation

HRID 1257873 reaction equation
O=[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)=[N:4][NH:3]1.P(Cl)(Cl)([Cl:20])=O>C(Cl)(Cl)Cl>[Cl:20][C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 59216301Methyl 4-(3-oxo-2,3-dihydro-1,2,4-triazin-6-yl)benzoate

Product 1

HCID 59216349Methyl 4-(3-chloro-1,2,4-triazin-6-yl)benzoateYield 17.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 4-(3-oxo-2,3-dihydro-1,2,4-triazin-6-yl)benzoate (13.4 g, 0.0580 mol), phosphoryl chloride (30 mL, 0.3 mol) in chloroform (50 mL) was refluxed (oil-bath temperature about 100° C.) for 2 h. After cooling to RT, the mixture was concentrated to remove excess phosphoryl chloride. The residue was dissolved in methylene chloride and poured into ice-water, and carefully neutralized with K2CO3. The organic layer was separated and the aqueous solution was extracted with methylene chloride. The combined organic phases were dried over Na2SO4, concentrated, and further purified by chromatography to afford the desired product (2.5 g, 17%). LCMS: (M+H)=249.9. 1H NMR (300 MHz, CDCl3): in ppm, 3.98 (s, 3H), 8.18 (d, 2H), 8.24 (d, 2H), 8.96 (s, 1H).

Workup

  1. temperatureAfter cooling to RT
  2. concentrationthe mixture was concentrated
  3. customto remove excess phosphoryl chloride
  4. dissolutionThe residue was dissolved in methylene chloride
  5. additionpoured into ice-water
  6. customThe organic layer was separated
  7. extractionthe aqueous solution was extracted with methylene chloride
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. concentrationconcentrated
  10. customfurther purified by chromatography

Sources & evidence

ORD record
ord-64ec7cf0da9648a88049208dcadc90a6
Source dataset
uspto-grants-2013_06
Patent number
US08461330B2

Reaction notes

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