Ethyl diazoacetate → (2-Bocamino-2-methyl-propoxy)-acetic acid

HRID 1602015Notes

Reaction equation

HRID 1602015 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:13])([CH3:12])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH:16][C:17]([O:19]CC)=[O:18])=[N-].C(=O)(O)[O-].[Na+]>ClCCCl.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:1]([O:5][C:6]([NH:8][C:9]([CH3:13])([CH3:12])[CH2:10][O:11][CH2:16][C:17]([OH:19])=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 12192Ethyl diazoacetateHCID 516892Sodium BicarbonateHCID 14578673tert-butyl N-(1-hydroxy-2-methylpropan-2-yl)carbamate

Product 1

HCID 10776871(2-Bocamino-2-methyl-propoxy)-acetic acidYield 38.9%

Reagents, catalysts & solvents 2

HCID 21674Acetic acid, rhodium(2+) saltCatalyst2×HCID 111,2-DichloroethaneSolvent

Procedure

A solution of 2-tert-butoxycarbonylamino-2-methylpropanol (5.0 g, 26 mmol) and rhodium(II)acetate (90 mg) in 1,2-dichloroethane (500 ml) was heated to 80° C. Then ethyl diazoacetate (4.0 g, 35 mmol) was added over a period of 1 h, and the mixture was stirred at reflux for 3 h. Another portion of rhodium(II)acetate (90 mg) was added and the mixture was refluxed for another 5 h. The mixture was cooled overnight and saturated sodium bicarbonate (500 ml) was added, the phases were separated and the organic layer was washed with saturated sodium bicarbonate (2×200 ml), dried (magnesium sulfate) and concentrated in vacuo. The obtained product was dissolved in 1M lithium hydroxide in methanol/water 3:1 (200 ml) and stirred overnight. The solvent was removed in vacuo, water was added (pH>9) and the mixture was washed with ether (200 ml). Then 1M hydrochloric acid was added until pH<4 and the mixture was extracted with ethyl acetate (200 ml), dried (magnesium sulfate) and concentrated in vacuo to give 2.5 g of (2-tert-butoxycarbonylamino-2-methylpropoxy)acetic acid.

Workup

  1. temperatureat reflux for 3 h
  2. temperaturethe mixture was refluxed for another 5 h
  3. temperatureThe mixture was cooled overnight
  4. customthe phases were separated
  5. washthe organic layer was washed with saturated sodium bicarbonate (2×200 ml)
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe obtained product was dissolved in 1M lithium hydroxide in methanol/water 3:1 (200 ml)
  9. stirringstirred overnight
  10. customThe solvent was removed in vacuo, water
  11. additionwas added (pH>9)
  12. washthe mixture was washed with ether (200 ml)
  13. additionThen 1M hydrochloric acid was added until pH<4
  14. extractionthe mixture was extracted with ethyl acetate (200 ml)
  15. dry with materialdried (magnesium sulfate)
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7f822dabc3ed4fa4923b93cca43667db
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

Loading…