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

HRID 366166Notes

Reaction equation

HRID 366166 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+]>ClC(Cl)C.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 38.2%

Reagents, catalysts & solvents 2

HCID 21674Acetic acid, rhodium(2+) saltCatalyst2×HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 2-t-butoxycarbonylamino-2-methylpropanol (5.0 g, 26.46 mmol) and rhodium(II)acetate (90 mg) in dichloroethane (500 ml) was heated to 80° C. Then ethyl diazoacetate (4.0 g, 34.78 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 layers were separated and the organic layer was washed twice with saturated sodium bicarbonate (2×200 ml) and dried (magnesium sulfate) and concentrated in vacuo. The obtained product was dissolved in 1 M lithium hydroxide in methanol/water 3:1 (200 ml) and stirred overnight. The solvent was removed in vacuo to a minimum, water (50 ml) was added (pH>9) and the mixture was washed with ether (100 ml). Then 1 M hydrochloric acid was added until pH<4 and the mixture was extracted with ethyl acetate (100 ml) and the combined organic layers were dried (magnesium sulfate) and concentrated in vacuo to give 2.5 g of (2-t-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 layers were separated
  5. washthe organic layer was washed twice with saturated sodium bicarbonate (2×200 ml)
  6. dry with materialdried (magnesium sulfate)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe obtained product was dissolved in 1 M lithium hydroxide in methanol/water 3:1 (200 ml)
  9. stirringstirred overnight
  10. customThe solvent was removed in vacuo to a minimum, water (50 ml)
  11. additionwas added (pH>9)
  12. washthe mixture was washed with ether (100 ml)
  13. additionThen 1 M hydrochloric acid was added until pH<4
  14. extractionthe mixture was extracted with ethyl acetate (100 ml)
  15. dry with materialthe combined organic layers were dried (magnesium sulfate)
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-740cae675f8d40efbb58e10fbe3d0876
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Reaction notes

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