Citric Acid → Methyl 2-hydroxy-4-((1-(methylsulfonyl)piperidin-4-yl)oxy)benzoate

HRID 454486

Reaction equation

HRID 454486 reaction equation
C(=O)([O-])[O-].[K+].[K+].CS([O:11][CH:12]1[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]1)(=O)=O.[OH:22][C:23]1[CH:32]=[C:31](O)[CH:30]=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26].[I-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C.CN(C)C(=O)C>[OH:22][C:23]1[CH:32]=[C:31]([O:11][CH:12]2[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]2)[CH:30]=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 5238Sodium IodideHCID 11430Potassium Carbonate2×HCID 16523Methyl 2,4-DihydroxybenzoateHCID 222730651-(Methylsulfonyl)piperidin-4-yl methanesulfonate2×

Product 1

HCID 66990733Methyl 2-hydroxy-4-((1-(methylsulfonyl)piperidin-4-yl)oxy)benzoateYield 38.8%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

Potassium carbonate (0.31 g) and 1-(methylsulfonyl)piperidin-4-yl methanesulfonate (0.46 g) were added to an N,N-dimethylacetamide (5 mL) solution of methyl 2,4-dihydroxybenzoate (0.25 g), followed by stirring at 90° C. for 1 hour. The reaction mixture was cooled to room temperature, and then sodium iodide (0.045 g) was added thereto, followed by stirring at 90° C. for 1 hour. The reaction mixture was cooled to room temperature, and then potassium carbonate (0.10 g) and 1-(methylsulfonyl)piperidin-4-yl methanesulfonate (0.12 g) were added thereto, followed by stirring at 90° C. for 1 hour. The reaction mixture was cooled to room temperature, and then a 10% aqueous solution of citric acid and ethyl acetate were added thereto. The organic layer was separated, washed with a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride sequentially, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-60% hexane/ethyl acetate] to obtain 0.19 g of methyl 2-hydroxy-4-((1-(methylsulfonyl)piperidin-4-yl)oxy)benzoate as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringby stirring at 90° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringby stirring at 90° C. for 1 hour
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customThe organic layer was separated
  7. washwashed with a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride sequentially
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 90-60% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-59079404656a4ed3b8de3bd56c773b8b
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Linked notes

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