Pyridine → N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-N-methylbutanamide

HRID 979246Notes

Reaction equation

HRID 979246 reaction equation
[S:1](Cl)Cl.[CH3:4][NH:5][C:6](=[O:10])[CH2:7][CH2:8][CH3:9].N1C=CC=CC=1.[F:17][C:18]1[CH:24]=[C:23]([O:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][C:27]=2[Cl:36])[CH:22]=[CH:21][C:19]=1[NH2:20]>ClCCl.C(OCC)C.C(N(CC)CC)C>[Cl:36][C:27]1[CH:28]=[C:29]([C:32]([F:34])([F:33])[F:35])[CH:30]=[CH:31][C:26]=1[O:25][C:23]1[CH:22]=[CH:21][C:19]([NH:20][S:1][N:5]([CH3:4])[C:6](=[O:10])[CH2:7][CH2:8][CH3:9])=[C:18]([F:17])[CH:24]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 25353Sulfur dichlorideHCID 28774N-MethylbutanamideHCID 15595105Benzenamine, 4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluoro-

Product 1

HCID 20183877N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-N-methylbutanamideYield 83.8%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent3×HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
10 °C

Procedure

A solution of sulphur dichloride (11.3 g) in dichloromethane (10 ml) was added over 20 minutes to a solution of N-methylbutanamide (10.1 g) in the same solvent (35 ml) with stirring, the temperature being maintained at 10° C. Stirring at this temperature was continued for a further 30 minutes after which time a solution of pyridine (8.7 g) in dichloromethane (15 ml) was added. The mixture was then stirred and allowed to warm to room temperature over 2 hours, then filtered. The solvent was stripped off and the residue extracted with diethyl ether. After filtration, solvent removal and distillation, 12.1 g of the sulphenyl chloride as an oil, boiling point 82°-84° C. at 13 mmHg, was obtained. 4.4 g of this oil was dissolved in diethyl ether (10 ml) and the resulting solution was added over 20 minutes to a mixture of the compound of Example 1 (7.6 g) and triethylamine (2.7 g) in diethyl ether (30 ml). After stirring for 30 minutes at room temperature, 150 ml diethyl ether was added, the resultant soution was washed three times with water, dried, stripped of solvent and purified by chromatography over silica using dichloromethane as eluant. 9.1 g of the desired product was obtained as a brown oil.

Workup

  1. stirringStirring at this temperature
  2. stirringThe mixture was then stirred
  3. temperatureto warm to room temperature over 2 hours
  4. filtrationfiltered
  5. extractionthe residue extracted with diethyl ether
  6. filtrationAfter filtration, solvent removal and distillation, 12.1 g of the sulphenyl chloride as an oil, boiling point 82°-84° C. at 13 mmHg
  7. customwas obtained
  8. stirringAfter stirring for 30 minutes at room temperature
  9. washthe resultant soution was washed three times with water
  10. customdried
  11. custompurified by chromatography over silica

Sources & evidence

ORD record
ord-3ddb8084f71e4fdb8f92805fa8f5869e
Source dataset
uspto-grants-1987_05
Patent number
US04666942

Reaction notes

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