Reaction #84040

Reaction equation

Methyl chloroformate

NaOH

L-Leucine

sodium carbonate

→

(S)-2-(methoxycarbonylamino)-4-methylpentanoic acid

Conditions

Workup

1. 1
   Otherreach room temperature
2. 2
   OtherThe reaction mixture is separated with ether (3×50 mL)
3. 3
   Otherthe aqueous layer is contained in a round bottom flask
4. 4
   Temperaturecooled over an ice-water bath
5. 5
   workup.ADDITIONConcentrated HCl (aq) is added drop wise until pH 2
6. 6
   Otheris brought to room temperature
7. 7
   Extractionextracted with 2-Me-THF (3×50 mL)
8. 8
   Dryingdried (MgSO4)
9. 9
   Otherthe solids removed by filtration
10. 10
    Otherthe solvents of the filtrate removed under reduced pressure
11. 11
    OtherThe 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
    Otherthe solvent were removed in vacuum
14. 14
    Otherresulting in N-methoxycarbonyl-L-leucine (1.9 g, 32%)

Procedure

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%).

Source