Water → Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinate

HRID 246929Notes

Reaction equation

HRID 246929 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].[CH3:22][C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[C:24]=1[S:31](Cl)(=[O:33])=[O:32].C(N(CC)CC)C.O>C(Cl)Cl.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][S:31]([C:24]2[C:25]([CH3:30])=[CH:26][C:27]([CH3:29])=[CH:28][C:23]=2[CH3:22])(=[O:33])=[O:32])[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 130462-Mesitylenesulfonyl chlorideHCID 178498343Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate

Product 1

HCID 13821758Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinateYield 81.9%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

In 10 ml of methylene chloride was suspended 500 mg of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate, and to the resulting suspension were added 440 mg of 2,4,6-trimethylbenzenesulfonyl chloride and 220 mg of triethylamine, after which the resulting mixture was subjected to reaction at room temperature for 3 hours. To this solution was added 15 ml of water, and the organic layer was separated, washed with 15 ml of water, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 15 ml of diethyl ether, after which crystals were collected by filtration to obtain 660 mg (yield 81.9%) of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinate having a melting point of 153°-155° C.

Workup

  1. customafter which the resulting mixture was subjected to reaction at room temperature for 3 hours
  2. customthe organic layer was separated
  3. washwashed with 15 ml of water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customto the crystalline material thus obtained
  7. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-eb13d8ba97bb4395b4985c1abae92c80
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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