Hydrochloric Acid → Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetate

HRID 246943Notes

Reaction equation

HRID 246943 reaction equation
Cl[C:2]1[C:15]([F:16])=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=O)=[C:4]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])[N:3]=1.C1([SH:32])C=CC=CC=1.C(N(CC)CC)C.Cl.[CH3:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46]>CN(C)C=O.O.C(OCC)(=O)C>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[NH:17][C:4]1[N:3]=[C:2]([C:43]2[CH:42]=[CH:41][CH:46]=[CH:45][CH:44]=2)[C:15]([F:16])=[CH:14][C:5]=1[C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[S:32]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 8058HexaneHCID 8471TriethylamineHCID 13849316Ethyl 2-[6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate

Product 1

HCID 20031433Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetateYield 94.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 1.5 ml of N,N-dimethylformamide was dissolved 150 mg of ethyl 2-[6-chloro-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate, and 70 mg of thiophenol and 60 mg of triethylamine were added thereto, after which the resulting mixture was subjected to reaction at room temperature for 1 hour. Subsequently, to the reaction mixture were added 20 ml of ethyl acetate and 10 ml of water, and the pH thereof was adjusted to 2.0 with 2N hydrochloric acid. The organic layer was separated, washed successively with 10 ml of water and 10 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 5 ml of n-hexane, after which crystals were collected by filtration to obtain 170 mg (yield 94.6%) of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetate. The physical properties of this compound were identical with those of the compound obtained in Example 19.

Workup

  1. additionwere added
  2. customafter which the resulting mixture was subjected to reaction at room temperature for 1 hour
  3. customThe organic layer was separated
  4. washwashed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed by distillation under reduced pressure
  7. customto the crystalline material thus obtained
  8. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-0c12b1860fa24f1aaecc58276fd1ba94
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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