Reaction #4858

Reaction equation

NMM

NMM

Racemic t-butoxycarbonyl 2,6-dimethyltyrosine

alanine methyl ester hydrochloride

→

mixture

Yield 98.9%

N-[(1,1-dimethylethoxy)carbonyl]-2,6dimethyl-DL-tyrosyl-D-alanine, methyl ester

Yield 98.9%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   Temperatureto reflux it
2. 2
   workup.ADDITION1.32 ml (10 mmoles) of IBCF were added to this stirred solution
3. 3
   Otherto rise to -15° C.
4. 4
   Otherlowered to -50° C.
5. 5
   workup.ADDITIONwas added to the solution
6. 6
   Temperatureto warm to room temperature
7. 7
   OtherThe majority of the CH2Cl2 was removed under reduced pressure
8. 8
   workup.ADDITIONEthyl acetate (200 ml) was added
9. 9
   Washthis solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O
10. 10
    Dryingdried over MgSO4
11. 11
    OtherRemoval of all solvent

Procedure

Racemic t-butoxycarbonyl 2,6-dimethyltyrosine (3.9 g, 10 mmoles) was dissolved in 30 ml of CH2Cl2 by adding 1.12 ml (10 mmoles) of NMM. After bringing this mixture to reflux it was cooled to -30° C. and 1.32 ml (10 mmoles) of IBCF were added to this stirred solution. The temperature was allowed to rise to -15° C. and then lowered to -50° C. (D) alanine methyl ester hydrochloride (1.54 g, 11 mmoles) was added to the solution followed by 1.3 ml (11 mmoles) of NMM. The mixture was allowed to warm to room temperature and stand for 16 hours. The majority of the CH2Cl2 was removed under reduced pressure. Ethyl acetate (200 ml) was added and this solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O and dried over MgSO4. Removal of all solvent gave 3.9 g of the mixture of diastereomers. Recrystallization of this material from Skelly B/CH2Cl2 produced 1.6 g (4.2 mmoles) of diastereomer F. Removal of the solvent from the filtrate gave 1.3 g (3.3 mmoles) of diastereomer S contaminated by less than 10% of diastereomer F.

Source