Pivaloyl chloride → Methyl 2-hydroxy-6-pivalamidobenzoate

HRID 715974Notes

Reaction equation

HRID 715974 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3](Cl)=[O:4].[NH2:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[C:10]=1[C:11]([O:13][CH3:14])=[O:12].C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C>[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[O:4]

Participants

6

Reactant 3

HCID 62493Pivaloyl chloride2×HCID 516892Sodium BicarbonateHCID 21514499Methyl 2-amino-6-hydroxybenzoate

Product 1

HCID 66686167Methyl 2-hydroxy-6-pivalamidobenzoateYield 64.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trimethylacetyl chloride (5.57 g) was added dropwise to a vigorously stirred mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 5.15 g) and sodium bicarbonate (7.76 g) in a mixture of water (40 mL) and ethyl acetate (100 mL) and the mixture was stirred for one hour. Further trimethylacetyl chloride (5.57 g) was added and the mixture stirred overnight. The organic layer was separated, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was triturated with pentane. The solid was collected by filtration and purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25% to give methyl 2-(2,2-dimethyl-propionylamino)-6-hydroxy-benzoate (4.96 g) as a white solid.

Workup

  1. stirringthe mixture stirred overnight
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was triturated with pentane
  7. filtrationThe solid was collected by filtration
  8. custompurified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-25%

Sources & evidence

ORD record
ord-0afc0b8d38c54f139c24c9e0b0e6914d
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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