Triethylamine → HCID 9951428, compound

HRID 2299224Notes

Reaction equation

HRID 2299224 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C(N(CC)CC)C.Cl[S:18]([C:21]1[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][C:22]=1[C:29]([O:31][CH2:32][CH3:33])=[O:30])(=[O:20])=[O:19]>C(OCC)(=O)C>[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH:4][S:18]([CH:21]1[C:22]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:23][C:24]([CH3:27])([CH3:28])[CH2:25][CH2:26]1)(=[O:20])=[O:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 97092,4-DifluoroanilineHCID 21958036HCID 21958036, compound

Product 1

HCID 9951428HCID 9951428, compoundYield 24.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

Procedure

2,4-Difluoroaniline (1.51 g) was dissolved in ethyl acetate (33 ml) and the resultant solution was admixed with triethylamine (2.51 ml) with ice-cooling, and then treated dropwise with a solution of ethyl 2-chlorosulfonyl-5,5-dimethyl-1-cyclohexene-1-carboxylate (2.53 g) obtained in Reference Example 18 in ethyl acetate (17 ml). The reaction mixture was stirred under nitrogen flow at 0° C. for 30 minutes then at room temperature for 64.5 hours. The reaction mixture was diluted with ethyl acetate, and washed successively with water (120 ml), 0.5 N HCl (120 ml), water (120 ml×2) and saturated brine (120 ml). The ethyl acetate layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane=1/9→1/7). A desired fraction was concentrated under reduced pressure, and the residue was crystallized from a mixture of ethyl acetate and diisopropyl ether to yield ethyl 6-[N-(2,4-difluorophenyl)sulfamoyl]-3,3-dimethyl-1-cyclohexene-1-carboxylate (Compound 83; 0.83 g) as white crystals.

Workup

  1. temperaturecooling
  2. waitat room temperature for 64.5 hours
  3. washwashed successively with water (120 ml), 0.5 N HCl (120 ml), water (120 ml×2) and saturated brine (120 ml)
  4. dry with materialThe ethyl acetate layer was dried over magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane=1/9→1/7)
  7. concentrationA desired fraction was concentrated under reduced pressure
  8. customthe residue was crystallized from a mixture of ethyl acetate and diisopropyl ether

Sources & evidence

ORD record
ord-a339a105c4cc4366991cb600460927f2
Source dataset
uspto-grants-2002_12
Patent number
US06495604B1

Reaction notes

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