Water → 2-(((Tert-butoxy)carbonyl)amino)-3-methoxy-3-methylbutanoic acid

HRID 72046Notes

Reaction equation

HRID 72046 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:13]([OH:16])([CH3:15])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:17]I.[H-].[Na+].O>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([NH:8][CH:9]([C:13]([O:16][CH3:17])([CH3:15])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 13756005N-Boc-(+-)-2-amino-3-hydroxy-3-methylbutanoic acid

Product 1

HCID 231384102-(((Tert-butoxy)carbonyl)amino)-3-methoxy-3-methylbutanoic acidYield 94%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-tert-Butoxycarbonylamino-3-hydroxy-3-methyl-butyric acid (1.0 g, 4.29 mmol) was dissolved in THF (14 mL) and cooled to 0° C. in an external ice/brine bath. MeI (2.13 mL, 34.3 mmol) was added at 0° C. Solid NaH (60% dispersion in mineral oil, 0.514 g, 12.87 mmol) was added slowly at 0° C. Upon completion of the addition, the solution was removed from the ice bath and allowed to warm to room temperature, and stirred. After 18 hours, the crude reaction mixture was diluted in ethyl acetate and water was added slowly with stirring. The quenched mixture was concentrated in vacuo and partitioned between diethyl ether and water. The ether layer was extracted with sodium bicarbonate twice. The combined bicarbonate layers were acidified with aqueous citric acid to pH 3 and extracted three times with ethyl acetate. The combined ethyl acetate layers were washed with water, sodium thiosulfate, water, dried with sodium sulfate and concentrated to yield 2-tert-Butoxycarbonylamino-3-methoxy-3-methyl-butyric acid (0.99 g, 94%) as an oil.

Workup

  1. additionUpon completion of the addition
  2. customthe solution was removed from the ice bath
  3. temperatureto warm to room temperature
  4. customthe crude reaction mixture
  5. stirringwith stirring
  6. concentrationThe quenched mixture was concentrated in vacuo
  7. custompartitioned between diethyl ether and water
  8. extractionThe ether layer was extracted with sodium bicarbonate twice
  9. extractionextracted three times with ethyl acetate
  10. washThe combined ethyl acetate layers were washed with water, sodium thiosulfate, water
  11. dry with materialdried with sodium sulfate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-db5f696c6e33465cbe4cbb21a7ef267b
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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