HCID 9863761, compound → HCID 21958068, compound

HRID 2299219Notes

Reaction equation

HRID 2299219 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH:12]2[C:17]([C:18]([O:20][CH2:21]C)=[O:19])=[CH:16][CH2:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[C:4]([F:23])[CH:3]=1>CO.S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([CH:12]2[C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH2:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[C:4]([F:23])[CH:3]=1

Participants

4

Reactant 1

HCID 9863761HCID 9863761, compound2×

Product 1

HCID 21958068HCID 21958068, compoundYield 24.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1118Sulfuric AcidSolvent

Procedure

To a solution of ethyl 6-[N-(4-chloro-2-fluorophenyl)sulfamoyl]-1-cyclohexene-1-carboxylate obtained in Example 1 (Compound 1, 250 mg) in methanol (5 ml), concentrated sulfuric acid (0.2 ml) was added and the mixture was stirred under reflux for 8 days hours. The reaction mixture was concentrated under reduced pressure and diluted with ethyl acetate (30 ml) and washed with water (30 ml). The ethyl acetate layer was washed with water (30 ml×2) and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was ,subjected to silica gel chromatography (eluent: ethyl acetate/hexane=1/4) and desired fractions were concentrated under reduced pressure. The residue was purified by an ODS column chromatography (eluent: methanol/water=4/1) and then crystallized from diisopropyl ether to yield methyl 6-[N-(4-chloro-2-fluorophenyl)sulfamoyl]-1-cyclohexene-1-carboxylate (Compound 24, 58 mg) as colorless prism-like crystals.

Workup

  1. temperatureunder reflux for 8 days hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with ethyl acetate (30 ml)
  4. washwashed with water (30 ml)
  5. washThe ethyl acetate layer was washed with water (30 ml×2)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. concentrationdesired fractions were concentrated under reduced pressure
  9. customThe residue was purified by an ODS column chromatography (eluent: methanol/water=4/1)
  10. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-84c2d105497247c58ae1ecaf6d253cc5
Source dataset
uspto-grants-2002_12
Patent number
US06495604B1

Reaction notes

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