Ethyl bromopyruvate → 2-(1-Benzyloxycarbonylamino-cyclopropyl)-oxazole-4-carboxylic acid ethyl ester

HRID 1040493Notes

Reaction equation

HRID 1040493 reaction equation
[CH2:1]([O:8][C:9](=[O:17])[NH:10][C:11]1([C:14](=[O:16])[NH2:15])[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].[CH2:23]([O:25][C:26](=[O:31])[C:27](=O)[CH2:28]Br)[CH3:24]>C1COCC1>[CH2:23]([O:25][C:26]([C:27]1[N:15]=[C:14]([C:11]2([NH:10][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:17])[CH2:12][CH2:13]2)[O:16][CH:28]=1)=[O:31])[CH3:24]

Participants

5

Reactant 3

HCID 66144Ethyl bromopyruvateHCID 516892Sodium BicarbonateHCID 13676801(1-Carbamoyl-cyclopropyl)-carbamic acid benzyl ester

Product 1

HCID 584312412-(1-Benzyloxycarbonylamino-cyclopropyl)-oxazole-4-carboxylic acid ethyl esterYield 48.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (1-carbamoyl-cyclopropyl)-carbamic acid benzyl ester (3.0 g, 8.1 mmol) in THF (100 mL) was added NaHCO3 (9.7 g, 120 mmol) and 3-bromo-2-oxo-propionic acid ethyl ester (8.1 mL, 64.0 mmol). The reaction was heated at 70° C. for 15 h. The resulting orange suspension was filtered through celite and concentrated under reduced pressure. The resulting orange oil was dissolved in THF (10 mL) and to this was added trifluoroacetic anhydride (1 mL). The mixture was stirred at room temperature for 24 h. The reaction was quenched with satd NaHCO3 and extracted with EtOAc (3×50 mL). The combined extracts were washed with water, brine and dried with MgSO4. The mixture was filtered, concentrated and purified by reverse phase HPLC. The combined HPLC fractions were extracted with EtOAc (3×100 mL). The extracts were washed with water, brine and dried with MgSO4. The mixture was filtered and concentrated to give 2-(1-benzyloxycarbonylamino-cyclopropyl)-oxazole-4-carboxylic acid ethyl ester (1.3 g, 3.9 mmol) as a white solid.

Workup

  1. filtrationThe resulting orange suspension was filtered through celite and
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe resulting orange oil was dissolved in THF (10 mL)
  4. additionto this was added trifluoroacetic anhydride (1 mL)
  5. customThe reaction was quenched with satd NaHCO3
  6. extractionextracted with EtOAc (3×50 mL)
  7. washThe combined extracts were washed with water, brine
  8. dry with materialdried with MgSO4
  9. filtrationThe mixture was filtered
  10. concentrationconcentrated
  11. custompurified by reverse phase HPLC
  12. extractionThe combined HPLC fractions were extracted with EtOAc (3×100 mL)
  13. washThe extracts were washed with water, brine
  14. dry with materialdried with MgSO4
  15. filtrationThe mixture was filtered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-66b35dc5d9da44298e4688d163438bfd
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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