Water → Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetate

HRID 232464Notes

Reaction equation

HRID 232464 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:23]=[C:22]([OH:24])[C:21]([F:25])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13].[CH3:26][C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[C:29]([CH3:34])[C:28]=1[S:35](Cl)(=[O:37])=[O:36].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:23]=[C:22]([O:24][S:35]([C:28]2[C:29]([CH3:34])=[CH:30][C:31]([CH3:33])=[CH:32][C:27]=2[CH3:26])(=[O:37])=[O:36])[C:21]([F:25])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 130462-Mesitylenesulfonyl chlorideHCID 178472175Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinoyl]acetate

Product 1

HCID 13849317Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetateYield 85.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

In 4 ml of methylene chloride was dissolved 400 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinoyl]acetate, and 300 mg of 2,4,6-trimethylbenzenesulfonyl chloride and 150 mg of triethylamine were added thereto with ice-cooling, after which the resulting mixture was subjected to reaction at room temperature for 2 hours. Subsequently, to the reaction mixture were added 4 ml of methylene chloride and 4 ml of water, and the organic layer was separated, washed successively with 4 ml of water and 4 ml of saturated aqueous sodium chloride solution, 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 2 ml of diethyl ether, after which crystals were collected by filtration to obtained 520 mg (yield 85.8%) of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetate. The physical properties of this compound were identical with those of the compound obtained in Example 19.

Workup

  1. additionwere added
  2. temperaturewith ice-cooling
  3. customafter which the resulting mixture was subjected to reaction at room temperature for 2 hours
  4. customthe organic layer was separated
  5. washwashed successively with 4 ml of water and 4 ml of saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customto the crystalline material thus obtained
  9. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-e4c0533900e2449aa35b7f22b28cc842
Source dataset
uspto-grants-1989_07
Patent number
US04851535

Reaction notes

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