Methyl iodide → O-Benzyl-N-(tert-butoxycarbonyl)-N-methyl-L-serine

HRID 1062312Notes

Reaction equation

HRID 1062312 reaction equation
[C:1]([NH:8][C@H:9]([C:19]([OH:21])=[O:20])[CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:22]I.[H-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[CH2:12]([O:11][CH2:10][C@H:9]([N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH3:22])[C:19]([OH:21])=[O:20])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 90234L-Serine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-

Product 1

HCID 46737465O-Benzyl-N-(tert-butoxycarbonyl)-N-methyl-L-serine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N-Boc-O-Benzyl-L-Serine (8.86 g, 30.0 mmol) was dissolved in tetrahydrofuran (94 mL) and the resultant solution was cooled with a 0° C. ice bath. Methyl iodide (15.0 mL, 241 mmol) was added in one portion. After 5 min, sodium hydride (60% dispersion in mineral oil, 3.6 g, 90 mmol) was added in three portions during 10 min. The resultant reaction mixture was stirred under nitrogen for 76 h while the cooling bath temperature was maintained at 0° C. The reaction mixture was diluted with cold (0-5° C.) ethyl acetate (150 mL) and water (1.5 mL) was added dropwise over 10 min. The cooling bath temp was allowed to slowly warm to ambient temperature overnight. The reaction mixture was concentrated to a viscous oil on a rotary evaporator without heating. The residue was partitioned between ether (100 mL) and water (300 mL). The ethereal layer was further washed with saturated aqueous sodium bicarbonate (150 mL). The combined aqueous portions were acidified to pH 3 using aqueous citric acid (2 M) and were extracted with ethyl acetate (3×150 mL). The combined extracts were washed with water (2×150 mL) and 5% aqueous sodium thiosulfate (150 mL), dried over magnesium sulfate and concentrated on a rotary evaporator (without heating) to afford (S)-3-Benzyloxy-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid as viscous, colorless oil (8.98 g).

Workup

  1. customThe resultant reaction mixture
  2. additionwas added dropwise over 10 min
  3. temperatureto slowly warm to ambient temperature overnight
  4. concentrationThe reaction mixture was concentrated to a viscous oil on a rotary evaporator
  5. temperaturewithout heating
  6. customThe residue was partitioned between ether (100 mL) and water (300 mL)
  7. washThe ethereal layer was further washed with saturated aqueous sodium bicarbonate (150 mL)
  8. extractionwere extracted with ethyl acetate (3×150 mL)
  9. washThe combined extracts were washed with water (2×150 mL) and 5% aqueous sodium thiosulfate (150 mL)
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated on a rotary evaporator (without heating)

Sources & evidence

ORD record
ord-b4aefdd283794d37bb01ff7213249751
Source dataset
uspto-grants-2005_11
Patent number
US06960614B2

Reaction notes

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