Reaction #4860

Reaction equation

3-phenylpropylamine

CH2Cl2

title compound

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

NMM

→

title product

N-[(1,1-dimethylethoxy)carbonyl]-2,6-dimethyl-tyrosyl-N-(3-phenylpropyl)-D-alaninamide

Solvents

EtOAc

Conditions

Workup

1. 1
   workup.ADDITIONTo this solution was added 5.7 g (43.6 mmole) of IBCF
2. 2
   Temperaturethe mixture warmed to 10° C
3. 3
   TemperatureThe solution was then cooled to -25° C.
4. 4
   Otherthe reaction
5. 5
   Temperatureto warm to room temperature
6. 6
   Extractionextracted with three 100 ml portions of 0.5N KHSO4
7. 7
   ExtractionThe combined aqueous washes were extracted with 100 ml of EtOAc
8. 8
   WashThe combined organic was then washed with one 150 ml portion of brine
9. 9
   Dryingbefore drying it over Na2SO4
10. 10
    OtherAll solvent was removed under reduced pressure

Procedure

A CH2Cl2 solution (100 ml) of the title compound from Example 9, (16.6 g, 43.6 mmole) was charged with 4.4 g (43.6 mmoles) of NMM and cooled to -45° C. To this solution was added 5.7 g (43.6 mmole) of IBCF and the mixture warmed to 10° C. The solution was then cooled to -25° C. before adding 7.4 g (54.5 mmole) of 3-phenylpropylamine. After allowing the reaction to warm to room temperature and stand overnight, it was diluted with 300 ml of EtOAc and extracted with three 100 ml portions of 0.5N KHSO4. The combined aqueous washes were extracted with 100 ml of EtOAc and this extract was combined with the original organic phase. The combined organic was then washed with one 150 ml portion of brine before drying it over Na2SO4. All solvent was removed under reduced pressure to give the title product as a foam. This material was chromatographed to give 10 g (46%) of a compound identical to diastereomer S of Example 3.

Source