Acetic Acid → Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate

HRID 246925Notes

Reaction equation

HRID 246925 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]([OH:20])[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13].[N+](=[CH2:24])=[N-].C(O)(=O)C>O1CCCC1.C(OCC)C>[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:20][CH3:24])[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 9550DiazomethaneHCID 178498343Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate

Product 1

HCID 13821754Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinateYield 71.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

In 6 ml of tetrahydrofuran was dissolved 200 mg of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate, and a solution of about 40 mg of diazomethane in diethyl ether was added to the resulting solution with ice-cooling, after which the resulting mixture was subjected to reaction at room temperature for 30 minutes. Subsequently, acetic acid was added until foaming was not caused in the reaction mixture, after which the solvent was removed by distillation under reduced pressure. The crystals thus obtained were washed with 6 ml of isopropyl alcohol to obtain 150 mg (yield 71.6%) of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate having a melting point of 160°-161° C.

Workup

  1. temperaturecooling
  2. customafter which the resulting mixture was subjected to reaction at room temperature for 30 minutes
  3. customafter which the solvent was removed by distillation under reduced pressure
  4. customThe crystals thus obtained
  5. washwere washed with 6 ml of isopropyl alcohol

Sources & evidence

ORD record
ord-81663399dfc647109cbb253792c8c974
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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