Sulfuric Acid → 4-(Methylsulfonyl)phenol

HRID 2070230Notes

Reaction equation

HRID 2070230 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].[CH3:18][CH:19]([CH3:39])[C:20]([O:22][CH2:23][CH2:24][O:25][C:26]([O:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=1)=[O:27])=[O:21].S(=O)(=O)(O)O>C(#N)C.COC(C)(C)C.O>[CH3:18][CH:19]([CH3:39])[C:20]([O:22][CH2:23][CH2:24][O:25][C:26]([NH:1][CH2:2][CH:3]1[CH2:4][CH2:5][CH:6]([C:9]([OH:11])=[O:10])[CH2:7][CH2:8]1)=[O:27])=[O:21].[CH3:38][S:35]([C:32]1[CH:33]=[CH:34][C:29]([OH:28])=[CH:30][CH:31]=1)(=[O:36])=[O:37]

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 11430Potassium CarbonateHCID 67352456[4-(Methylsulfonyl)phenoxycarbonyloxy]ethyl 2-methylpropanoateHCID 178511262HCID 178511262, compound

Product 2

HCID 1233504-(Methylsulfonyl)phenolHCID 672943074-({[(2-Methylpropanoyloxy)ethoxy]carbonylamino}methyl)cyclohexanecarboxylic Acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Trans-4-(Aminomethyl)-cyclohexanecarboxylic acid (0.94 g) and water (25 mL) were charged to a vessel at room temperature. Potassium carbonate (0.8 g) was added in one portion and the mixture was stirred at room temperature for 5 minutes. A solution of [4-(methylsulfonyl)phenoxycarbonyloxy]ethyl 2-methylpropanoate D3 (1.6 g) in acetonitrile (25 mL) was added. After 6 hours, tert-butyl methyl ether (50 mL) was added and the reaction mixture was cooled to 5-10° C. A solution of 5% aqueous sulfuric acid was added to adjust the pH to approximately 3. The mixture was then warmed to room temperature and stirred for 10 minutes. The organic layer was washed with water (3×10 mL) and evaporated to yield the title compound as an orange oil with 4-(methylsulfonyl)phenol as an impurity. Tert-butyl methyl ether (10 mL) and methylcyclohexane (5 mL) were added and the mixture was heated at 50° C. for 10 minutes. The mixture was then cooled to 40° C. over a period of 2 hours. The crystallization solution was seeded with 4-({[(2-methylpropanoyloxy)ethoxy]carbonylamino}methyl)cyclohexanecarboxylic acid (10 mg) and then stirred for 2 hours. The white, thick slurry was filtered and dried under vacuum at room temperature to provide 1 g of the title compound E2.

Workup

  1. waitAfter 6 hours
  2. temperaturethe reaction mixture was cooled to 5-10° C
  3. temperatureThe mixture was then warmed to room temperature
  4. stirringstirred for 10 minutes
  5. washThe organic layer was washed with water (3×10 mL)
  6. customevaporated

Sources & evidence

ORD record
ord-2a61272f13eb4f86b2b7453c5a60f884
Source dataset
uspto-grants-2012_10
Patent number
US08299291B2

Reaction notes

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