Phosphorus oxychloride → Methyl 6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinate

HRID 246928Notes

Reaction equation

HRID 246928 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:19]=[C:18](O)[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13].P(Cl)(Cl)(Cl)(Cl)[Cl:23].P(Cl)(Cl)(Cl)=O>O>[Cl:23][C:18]1[C:17]([F:21])=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])[N:19]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 178498343Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate

Product 1

HCID 13849310Methyl 6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinateYield 34.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 9.5 g of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate, 26.5 g of phosphorus pentachloride and 46.9 g of phosphorus oxychloride was subjected to reaction at 70°-80° C. for 4 hours. Subsequently, the reaction mixture was gradually added to 285 ml of water, and the crystals thus deposited were collected by filtration and then washed with 57 ml of water. The crystals thus obtained were purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene] to obtain 3.5 g (yield 34.7%) of methyl 6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinate having a melting point of 137°-139° C.

Workup

  1. customwas subjected to reaction at 70°-80° C. for 4 hours
  2. filtrationthe crystals thus deposited were collected by filtration
  3. washwashed with 57 ml of water
  4. customThe crystals thus obtained
  5. customwere purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene]

Sources & evidence

ORD record
ord-f06a540d9f43431b833f97306d268ac2
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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