Pivaloyl chloride → Methyl 2-hydroxy-6-pivalamidobenzoate

HRID 927935Notes

Reaction equation

HRID 927935 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+]>C(OCC)(=O)C.O>[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 chloride3×HCID 516892Sodium BicarbonateHCID 21514499Methyl 2-amino-6-hydroxybenzoate

Product 1

HCID 66686167Methyl 2-hydroxy-6-pivalamidobenzoateYield 96.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Trimethylacetyl chloride (3.69 g) was added to a mixture of methyl 2-amino-6-hydroxybenzoate (prepared according to Comess et al, US2004 0167128, 3.99 g) and sodium bicarbonate (2.57 g) in ethyl acetate (77 mL) and water (18 mL). The reaction mixture was stirred at room temperature for 1 hour. A further amount of trimethylacetyl chloride (1.85 g) was added and the mixture was stirred for 1 hour. A further amount of trimethylacetyl chloride (0.920 g) was added and the mixture was stirred for 30 minutes. The mixture was diluted with ethyl acetate, the layers were separated and the organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and 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-(2,2-dimethylpropionylamino)-6-hydroxybenzoate (5.79 g) as a white solid.

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. stirringthe mixture was stirred for 30 minutes
  3. customthe layers were separated
  4. dry with materialthe organic layer was dried (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-fc6ed9f119ab41978714baf8ab68cf26
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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