Methanol → 2-Acetylamino-5-(3-piperidin-1-ylpropoxy)benzoic acid methyl ester

HRID 1157447Notes

Reaction equation

HRID 1157447 reaction equation
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13]OS(C)(=O)=O)[CH:7]=[CH:6][C:5]=1[NH:19][C:20](=[O:22])[CH3:21].[NH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C([O-])([O-])=O.[K+].[K+].CO>C(#N)C>[NH4+:19].[OH-:2].[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][CH2:13][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:7]=[CH:6][C:5]=1[NH:19][C:20](=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 887MethanolHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 866229032-Acetylamino-5-(3-methanesulfonyloxypropoxy)benzoic acid methyl ester

Product 2

HCID 14923Ammonium HydroxideHCID 685239932-Acetylamino-5-(3-piperidin-1-ylpropoxy)benzoic acid methyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of the crude 2-acetylamino-5-(3-methanesulfonyloxypropoxy)benzoic acid methyl ester, piperidine (1.28 mL, 12.9 mmol) and K2CO3 (1.07 g, 7.7 mmol) in acetonitrile (12 mL) was heated at reflux temperature for 16 h. This reaction mixture was concentrated in vacuo and the crude residue partitioned between dichloromethane and water. The aqueous was extracted with dichloromethane (3×50 mL) and the combined organics washed with brine (1×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by chromatography on silica gel with dichloromethane:methanol:NH4OH (aq.) (180:19:1, v/v) as eluent to provide 2-acetylamino-5-(3-piperidin-1-ylpropoxy)benzoic acid methyl ester (526 mg, 1.6 mmol, 61% from 2-acetylamino-5-(3-hydroxypropoxy)benzoic acid methyl ester).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 16 h
  3. concentrationThis reaction mixture was concentrated in vacuo
  4. customthe crude residue partitioned between dichloromethane and water
  5. extractionThe aqueous was extracted with dichloromethane (3×50 mL)
  6. washthe combined organics washed with brine (1×50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel with dichloromethane

Sources & evidence

ORD record
ord-22168d4ded754f0f822220c5ba9d267c
Source dataset
uspto-grants-2010_10
Patent number
US07807686B2

Reaction notes

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