Beta-Propiolactone → Methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoate

HRID 1778394Notes

Reaction equation

HRID 1778394 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:11]([NH:13][C:14]1[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[C:15]=1[C:16]([O:18][CH3:19])=[O:17])=[O:12])([CH3:10])([CH3:9])[CH3:8].[C:25]1(=[O:29])[O:28][CH2:27][CH2:26]1.C(OCC)(=O)C>C1COCC1.O>[C:7]([C:11]([NH:13][C:14]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:27][CH2:26][C:25]([OH:29])=[O:28])[C:15]=1[C:16]([O:18][CH3:19])=[O:17])=[O:12])([CH3:10])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 2365Beta-PropiolactoneHCID 8857Ethyl AcetateHCID 23665647Potassium tert-butoxideHCID 66686167Methyl 2-hydroxy-6-pivalamidobenzoate2×

Product 1

HCID 66686291Methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoateYield 67.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (1.81 g) was added to a solution of methyl 2-tert-butylcarbonylamino-6-hydroxybenzoate (Intermediate 79, 4.06 g) in THF (30 mL) and the mixture was heated at 60° C. β-propiolactone (1.16 g) was added dropwise and the resultant mixture was heated at 60° C. for 25 minutes, then left to stand at room temperature overnight. Ethyl acetate and water were added and the layers were separated. The aqueous phase was extracted with more ethyl acetate and acidified to pH 2 using 1M hydrochloric acid. This was extracted with ethyl acetate, 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 50-100% to give methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoate (3.5 g) as a white solid.

Workup

  1. additionwas added dropwise
  2. waitleft
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted with more ethyl acetate
  5. extractionThis was extracted with ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 50-100%

Sources & evidence

ORD record
ord-c2bd644724044993ba4e696fa5de3724
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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