Sulfuric Acid → 4-(Methylsulfonyl)phenol

HRID 2070229Notes

Reaction equation

HRID 2070229 reaction equation
[CH3:1][CH:2]([CH2:4][C@H:5]([CH2:10][NH2:11])[CH2:6][C:7]([OH:9])=[O:8])[CH3:3].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>[CH3:3][CH:2]([CH3:1])[CH2:4][C@H:5]([CH2:10][NH:11][C:26]([O:25][CH2:24][CH2:23][O:22][C:20](=[O:21])[CH:19]([CH3:18])[CH3:39])=[O:27])[CH2:6][C:7]([OH:9])=[O:8].[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 5486971PregabalinHCID 67352456[4-(Methylsulfonyl)phenoxycarbonyloxy]ethyl 2-methylpropanoate

Product 2

HCID 1233504-(Methylsulfonyl)phenolHCID 86640714(3S)-5-Methyl-3-({[(2-methylpropanoyloxy)ethoxy]carbonylamino}methyl)hexanoic Acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Pregabalin (0.95 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 E1 as an orange oil with 4-(methylsulfonyl)phenol impurity. The crude product was purified by silica gel chromatography using ethyl acetate and hexane (4:6) to provide 1 g of the title compound E1 as a viscous oil.

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-fd5b76c55e5048b398d66d9b497510b7
Source dataset
uspto-grants-2012_10
Patent number
US08299291B2

Reaction notes

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