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

HRID 1099075Notes

Reaction equation

HRID 1099075 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 heated at reflux (oil-bath temperature about 100° C.) for 2 h. After cooling, the mixture was concentrated to remove excess phosphoryl chloride. The residue was dissolved in DCM. The solution was poured into ice-water, and carefully neutralized with K2CO3. The organic layer was separated. The aqueous solution was extracted with methylene chloride. The combined extracts were dried over Na2SO3. After filtration the filtrate was concentrated and further purified by flash column to afford the desired product (2.5 g, 17%). Analytical LCMS: (M+H)+=249.9. 1H NMR (300 MHz, CDCl3): 6 (ppm) 3.98 (s, 3H), 8.18 (d, 2H), 8.24 (d, 2H), 8.96 (s, 1H).

Workup

  1. temperaturewas heated
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated
  4. customto remove excess phosphoryl chloride
  5. dissolutionThe residue was dissolved in DCM
  6. additionThe solution was poured into ice-water
  7. customThe organic layer was separated
  8. extractionThe aqueous solution was extracted with methylene chloride
  9. dry with materialThe combined extracts were dried over Na2SO3
  10. filtrationAfter filtration the filtrate
  11. concentrationwas concentrated
  12. customfurther purified by flash column

Sources & evidence

ORD record
ord-324cc727c17f49048b7cfe56a93def64
Source dataset
uspto-grants-2012_03
Patent number
US08143251B2

Reaction notes

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