Pivaloyl chloride → Methyl 2-hydroxy-6-pivalamidobenzoate

HRID 2200345Notes

Reaction equation

HRID 2200345 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-1b5685dc8b9d4e0d84b343c8484b55d7
Source dataset
uspto-grants-2016_06
Patent number
US09359369B2

Reaction notes

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