Water → 2-Chloro-N-(2-chloro-3-pyridinyl)-N-methyl-3-pyridinecarboxamide

HRID 53509Notes

Reaction equation

HRID 53509 reaction equation
[Cl:1][C:2]1[C:7]([C:8]([NH:10][C:11]2[C:12]([Cl:17])=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-].[Na+].S(OC)(O[CH3:24])(=O)=O.O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]([C:8]([N:10]([C:11]2[C:12]([Cl:17])=[N:13][CH:14]=[CH:15][CH:16]=2)[CH3:24])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6497Dimethyl Sulfate2×HCID 14798Sodium HydroxideHCID 27475382-chloro-N-(2-chloropyridin-3-yl)pyridine-3-carboxamide

Product 1

HCID 100166002-Chloro-N-(2-chloro-3-pyridinyl)-N-methyl-3-pyridinecarboxamide

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 1140TolueneSolvent2×

Procedure

A four-necked round-bottomed flask, equipped with a mechanical stirrer, a dropping funnel, a thermometer and an efficient reflux condenser, was charged with 268.1 g (1.0 mol) of 2-chloro-N-(2-chloro-3-pyridinyl)-3-pyridinecarboxamide, 260 ml of 50% aqueous sodium hydroxide, 1500 ml of toluene and 8.0 g (0.0352 mol) of benzyltriethylammonium chloride. Stirring was begun and a solution of 134 ml (178.5 g, 1.415 mol) of dimethyl sulphate in 1 l of toluene was added dropwise over a period of about 3 hours, whereby the temperature rose to 50°-60° C. After the addition of dimethyl sulfate was complete, stirring at 60° C. was continued for a further 2 hours. The reaction mixture was cooled to room temperature and 1 l of water was added. The layers were separated, and the aqueous phase was extracted three times with 300-ml portions of toluene. The organic layers were combined and washed successively with 300 ml of water, 300 ml of 1% aqueous acetic acid and 300 ml of water. The combined organic extracts were dried over sodium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography on silica gel (0.2-0.5 mm) using as eluents successively toluene and ethyl acetate/cyclohexane/tetrahydrofuran 1/9/10 (v/v/v). The product obtained by evaporation of suitable fractions was recrystallized from acetonitrile/tert-butyl methyl ether 1/1 (v/v). It was highly soluble in dichloromethane, had a m.p. of 98°-101° C., and was identified to be 2-chloro-N-(2-chloro-3-pyridinyl)-N-methyl-3-pyridinecarboxamide. The yield was 232.5 g (82.5% of theory).

Workup

  1. customA four-necked round-bottomed flask, equipped with a mechanical stirrer, a dropping funnel
  2. customrose to 50°-60° C
  3. stirringstirring at 60° C.
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted three times with 300-ml portions of toluene
  6. washwashed successively with 300 ml of water, 300 ml of 1% aqueous acetic acid and 300 ml of water
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. customthe solvent was removed by distillation under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel (0.2-0.5 mm)
  10. customThe product obtained by evaporation of suitable fractions
  11. customwas recrystallized from acetonitrile/tert-butyl methyl ether 1/1 (v/v)

Sources & evidence

ORD record
ord-62b18c9fff754a76974216cf7bf26e97
Source dataset
uspto-grants-1997_04
Patent number
US05620974

Reaction notes

Loading…