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

HRID 1601993Notes

Reaction equation

HRID 1601993 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].C([O:16][C:17](=[O:21])[CH:18]=[N+]=[N-])C.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][CH2:18][C:17]([OH:21])=[O:16])=[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. Ethyldiazoacetate (4.0 g, 34.78 mmol) was slowly added over a period of 1 hr., and the mixture was stirred at reflux for 3 hr. Another 90 mg of rhodium(II)acetate was added and the mixture was refluxed for another 5 hr. The mixture was cooled overnight and 500 ml of saturated sodium bicarbonate was added, the yellow organic layer was separated and washed twice with saturated sodium bicarbonate (2×200 ml). The organic layer was dried over magnesium sulfate and concentrated in vacuo. The yellow oil was taken up in 200 ml of 1 M Lithium hydroxide in methanol:water (3:1) and stirred overnight. The solvent was removed in vacuo to a minimum and water was added (pH>9) and the mixture was washed with ether. Then 1M hydrogen chloride was added until pH<4 and the mixture was extracted with ethyl acetate, dried over magnesium sulfate and concentrated in vacuo to give 2.5 g (38%) of (2-t-butoxycarbonylamino-2-methylpropoxy) acetic acid as a clear oil.

Workup

  1. temperatureat reflux for 3 hr
  2. temperaturethe mixture was refluxed for another 5 hr
  3. temperatureThe mixture was cooled overnight
  4. customthe yellow organic layer was separated
  5. washwashed twice with saturated sodium bicarbonate (2×200 ml)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. stirringstirred overnight
  9. customThe solvent was removed in vacuo to a minimum and water
  10. additionwas added (pH>9)
  11. washthe mixture was washed with ether
  12. additionThen 1M hydrogen chloride was added until pH<4
  13. extractionthe mixture was extracted with ethyl acetate
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e13c5515a42a40f1815e221e6854a42f
Source dataset
uspto-grants-1999_11
Patent number
US05977178

Reaction notes

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