Pivaloyl chloride → Methyl 2-hydroxy-6-pivalamidobenzoate

HRID 1778395Notes

Reaction equation

HRID 1778395 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)(O)[O-].[Na+].[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]>C(OCC)(=O)C.O>[C:19]([C:18]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[O:23])([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 62493Pivaloyl chloride3×HCID 516892Sodium Bicarbonate2×HCID 21514499Methyl 2-amino-6-hydroxybenzoate

Product 1

HCID 66686167Methyl 2-hydroxy-6-pivalamidobenzoateYield 78.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 167128, 3.8 g) and sodium bicarbonate (2.52 g) in ethyl acetate (75 mL) and water (17.5 mL) was stirred at room temperature and pivaloyl chloride (3.51 g) was added dropwise. The resultant mixture was stirred at room temperature for 1 hour. A further amount of pivaloyl chloride (1.75 g) was added and the mixture was stirred at room temperature for 2.5 hours. A further amount of pivaloyl chloride (1 g) was added and the mixture was stirred at room temperature for 4 hours and 20 minutes. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added and the layers were separated. The organic phase was washed with brine, dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25% to give methyl 2-tert-butylcarbonylamino-6-hydroxybenzoate (4.46 g) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 4 hours and 20 minutes
  2. customthe layers were separated
  3. washThe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe residue was purified by chromatography on silica
  8. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-25%

Sources & evidence

ORD record
ord-930c6cc44e9940e0889d56266f0c752b
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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