反応 #84040

ord-39ad65ac9fc142649a7bb14dd4f1e092

反応方程式

COC(=O)Cl
Methyl chloroformate
[Na+].[OH-]
NaOH
CC(C)C[C@H](N)C(=O)O
L-Leucine
O=C([O-])[O-].[Na+].[Na+]
sodium carbonate
COC(=O)N[C@@H](CC(C)C)C(=O)O
(S)-2-(methoxycarbonylamino)-4-methylpentanoic acid

反応条件

温度
0°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他reach room temperature
  2. 2
    その他The reaction mixture is separated with ether (3×50 mL)
  3. 3
    その他the aqueous layer is contained in a round bottom flask
  4. 4
    温度cooled over an ice-water bath
  5. 5
    workup.ADDITIONConcentrated HCl (aq) is added drop wise until pH 2
  6. 6
    その他is brought to room temperature
  7. 7
    抽出extracted with 2-Me-THF (3×50 mL)
  8. 8
    乾燥dried (MgSO4)
  9. 9
    その他the solids removed by filtration
  10. 10
    その他the solvents of the filtrate removed under reduced pressure
  11. 11
    その他The compound was purified by silicagel chromatography with gradient elution from CH2Cl2 to CH2Cl2/MeOH/acetic acid 17/2/1
  12. 12
    workup.ADDITIONFractions containing product
  13. 13
    その他the solvent were removed in vacuum
  14. 14
    その他resulting in N-methoxycarbonyl-L-leucine (1.9 g, 32%)

実験手順

An aqueous NaOH (1M, 2.6 mL) solution is added, while stirring, to L-Leucine (4 g, 30.5 mmol) in a round bottom flask (250 mL). To this solution was added sodium carbonate (1.62 g, 15.2 mmol). The flask is cooled to 0° C. in an ice-water bath. Methyl chloroformate (2.6 mL, 33.5 mmol) is added drop wise and the reaction mixture is allowed to stir for 15 hours and reach room temperature. The reaction mixture is separated with ether (3×50 mL), and the aqueous layer is contained in a round bottom flask and cooled over an ice-water bath. Concentrated HCl (aq) is added drop wise until pH 2. The reaction mixture is brought to room temperature and extracted with 2-Me-THF (3×50 mL). The organic layers are pooled, dried (MgSO4), the solids removed by filtration, and the solvents of the filtrate removed under reduced pressure. The compound was purified by silicagel chromatography with gradient elution from CH2Cl2 to CH2Cl2/MeOH/acetic acid 17/2/1. Fractions containing product were combined and the solvent were removed in vacuum, resulting in N-methoxycarbonyl-L-leucine (1.9 g, 32%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09433609B2uspto-grants-2016_09