Methyl iodide → N-Boc-N-methyl-3-tert-butyl-L-alanine

HRID 2363559Notes

Reaction equation

HRID 2363559 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].IC.[H-].[Na+].[C:22](OCC)(=O)C>O1CCCC1>[C:1]([O:5][C:6]([N:8]([CH3:22])[C@@H:9]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 2755926(S)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acid

Product 1

HCID 86641984N-Boc-N-methyl-3-tert-butyl-L-alanine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(S)-2-(tert-Butoxycarbonylamino)-4,4-dimethylpentanoic acid (50 mg, 0.204 mmol) and iodomethane (0.102 mL, 1.631 mmol) were dissolved in tetrahydrofuran (2 mL) at 0° C. and sodium hydride (24.46 mg, 0.611 mmol) was added. The reaction was stirred at 0° C. for a half hour and at room temperature overnight. The reaction was cooled to 0° C. and ethyl acetate (1 mL) was added followed by dropwise quenching with water (2 mL). The solvent was removed in vacuo and the crude material was partitioned between ether and water. The ether layer was separated. The aqueous layer was acidified to pH˜5 using 1 N citric acid and extracted with ethyl acetate. The organic layer was washed with 1 N sodium thiosulfate and brine, dried (Na2SO4) and concentrated in vacuo. The compound was purified using a 4 g silica gel cartridge with a gradient of 0-3% methanol/dichloromethane over 20 minutes to give (S)-2-(tert-butoxycarbonyl(methyl)amino)-4,4-dimethylpentanoic acid: 1H NMR (300 MHz, DMSO-d6) δ ppm 12.63 (s, 1H), 4.57 (ddd, J=74.4, 9.5, 3.1, 1H), 2.69 (s, 3H), 1.83-1.53 (m, 2H), 1.39 (s, 9H), 0.89 (s, 9H); MS (DSI+) m/z 260 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customby dropwise quenching with water (2 mL)
  3. customThe solvent was removed in vacuo
  4. customthe crude material was partitioned between ether and water
  5. customThe ether layer was separated
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with 1 N sodium thiosulfate and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe compound was purified
  11. customover 20 minutes

Sources & evidence

ORD record
ord-23a1e8d7309143b5ba55f864e35aa951
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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