Hydrochloric Acid → Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinate

HRID 232456Notes

Reaction equation

HRID 232456 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](OS(C2C(C)=CC(C)=CC=2C)(=O)=O)[C:17]([F:33])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=O.C1([SH:40])C=CC=CC=1.C(N(CC)CC)C.Cl.[CH3:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54]>CN(C)C=O.O.C(OCC)(=O)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]([C:51]2[CH:50]=[CH:49][CH:54]=[CH:53][CH:52]=2)[C:17]([F:33])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[S:40]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 8058HexaneHCID 8471TriethylamineHCID 13821758Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinate

Product 1

HCID 54549062Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinateYield 90.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 39 ml of N,N-dimethylformamide was dissolved 3.89 g of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-(mesitylenesulfonyloxy)nicotinate, and to the resulting solution were added 1.34 g of thiophenol and 1.23 g of triethylamine, after which the resulting mixture was subjected to reaction at room temperature for 5 hours. Subsequently, 120 ml of ethyl acetate and 120 ml of water were added to the reaction mixture, and the pH of the mixture was adjusted to 2.0 with 2N hydrochloric acid. The organic layer was separated, washed successively with 80 ml of water and 80 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 20 ml of n-hexane, after which the crystals thus deposited were collected by filtration to obtain 2.85 g (yield 90.2%) of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinate having a melting point of 126°-128° C. The physical properties of this compound were identical with those of the compound obtained in Example 7.

Workup

  1. customafter which the resulting mixture was subjected to reaction at room temperature for 5 hours
  2. customThe organic layer was separated
  3. washwashed successively with 80 ml of water and 80 ml of saturated aqueous sodium chloride solution
  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 the crystals thus deposited were collected by filtration

Sources & evidence

ORD record
ord-dfce6356dc4b4e9b877bc1bfb8a92518
Source dataset
uspto-grants-1989_07
Patent number
US04851535

Reaction notes

Loading…