Methyl iodide → (2S)-2-(((1,1-Dimethylethoxy)carbonyl)methylamino)butanoic acid

HRID 1486100Notes

Reaction equation

HRID 1486100 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH3:16].[H-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]([CH3:16])[C@@H:9]([CH2:13][CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acid

Product 1

HCID 15689337(2S)-2-(((1,1-Dimethylethoxy)carbonyl)methylamino)butanoic acidYield 98.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of (S)-2-(tert-butoxycarbonylamino)butanoic acid (1.00 g, 4.92 mmol) in THF (16.4 ml) was added iodomethane (2.45 ml, 39.4 mmol) followed by sodium hydride (60% w/w dispersion in mineral oil, 590 mg, 14.8 mmol), portionwise. The reaction was allowed to warm to rt and stirred for 18 h, then cooled to 0° C., quenched by the careful addition of H2O, and washed with Et20. The aqueous layer was acidified by the addition of 1 M aq. HCl and extracted with Et20. The combined organic layers were washed with sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated to provide (S)-2-(tert-butoxycarbonyl(methyl)amino)butanoic acid (1.05 g, 98%) as a white solid. MS m/z 240 (MNa)+.

Workup

  1. temperaturecooled to 0° C.
  2. customquenched by the careful addition of H2O
  3. washwashed with Et20
  4. additionThe aqueous layer was acidified by the addition of 1 M aq. HCl
  5. extractionextracted with Et20
  6. washThe combined organic layers were washed with sat. aq. NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-6c1fde3b4e8a44ed87229af3094ba17b
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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