Chloroacetic Acid → 1-(4-{[4-(Methanesulfonyl)phenyl]methyl}piperidin-1-yl)ethan-1-one

HRID 1006378Notes

Reaction equation

HRID 1006378 reaction equation
S([O-])(O)=O.[Na+].[C:6](=O)(O)[O-].[Na+].[C:11]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=2)[CH2:16][CH2:15]1)(=[O:13])[CH3:12].ClCC(O)=O.[OH-].[Na+].Cl>O>[C:11]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:6])(=[O:29])=[O:28])=[CH:23][CH:22]=2)[CH2:16][CH2:15]1)(=[O:13])[CH3:12]

Participants

8

Reactant 6

HCID 300Chloroacetic AcidHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 226766334-[(1-Acetylpiperidin-4-yl)methyl]benzene-1-sulfonyl chlorideHCID 23665763Sodium Bisulfite

Product 1

HCID 226766261-(4-{[4-(Methanesulfonyl)phenyl]methyl}piperidin-1-yl)ethan-1-oneYield 81.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of sodium hydrogensulfite (4.57 g) and sodium bicarbonate (6.10 g) in water (40 mL) was added 4-[(1-acetyl-4-piperidinyl)methyl]benzenesulfonyl chloride (11.46 g) at 75° C. under stirring, and the mixture was stirred at 75° C. for an hour. Chloroacetic acid (5.14 g) and an aqueous solution of 50% sodium hydroxide (4.4 mL) was added to the reaction solution and stirred for 20 hours under reflux with heat. 1N Hydrochloric acid (20 ml) was added to the reaction mixture at 0° C., and the reaction mixture was extracted with ethyl acetate (60 mL, 30 mL). The organic phase was washed with saturated brine (10 mL×2), dried over magnesium sulfate (anhydrous), and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel 150 g, ethyl acetate/methanol=1/0→9/1). The objective fraction was concentrated under reduced pressure to give the title compound as a colorless oil (8.76 g).

Workup

  1. stirringthe mixture was stirred at 75° C. for an hour
  2. stirringstirred for 20 hours
  3. temperatureunder reflux
  4. temperaturewith heat
  5. extractionthe reaction mixture was extracted with ethyl acetate (60 mL, 30 mL)
  6. washThe organic phase was washed with saturated brine (10 mL×2)
  7. dry with materialdried over magnesium sulfate (anhydrous)
  8. concentrationconcentrated under reduced pressure
  9. concentrationThe objective fraction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-bdeb7dd5cf0142c09c6c8956d48ca725
Source dataset
uspto-grants-2004_09
Patent number
US06787650B1

Reaction notes

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