Reaction #55625

Reaction equation

carbobenzoxy-β-alanine

isobutylchloroformate

L-proline t-butyl ester hydrochloride

N-methylmorpholine

→

carbobenzoxy-β-alanyl-L-proline t-butyl ester

Solvents

triethylamine

dimethylformamide

tetrahydrofuran

Conditions

Workup

1. 1
   Otherthe resulting reaction mixture
2. 2
   workup.STIRRINGis stirred
3. 3
   workup.STIRRINGis thereafter stirred overnight
4. 4
   OtherThe solvent of the reaction mixture is evaporated in vacuo at 30°-35°
5. 5
   workup.DISSOLUTIONThe residue is dissolved in 800 ml
6. 6
   Washof ethyl acetate which is washed with (2×150 ml.) a 10% citric acid solution
7. 7
   DryingThe organic layer is dried with anhydrous magnesium sulfate
8. 8
   Otherthe solvent evaporated

Procedure

4.46 g. of carbobenzoxy-β-alanine is dissolved in 20 ml. of tetrahydrofuran and the resulting solution cooled to -10° C. With constant stirring of the solution, 2.4 ml. of N-methylmorpholine followed by 2.6 ml. of isobutylchloroformate are added and the resulting reaction mixture is stirred thereafter for approximately 5 minutes at -10° C. 4.16 g. of L-proline t-butyl ester hydrochloride in 20 ml. of dimethylformamide and 2.8 ml. of triethylamine is added to the reaction mixture which is thereafter stirred overnight, while slowly warming to room temperature. The solvent of the reaction mixture is evaporated in vacuo at 30°-35°. The residue is dissolved in 800 ml. of ethyl acetate which is washed with (2×150 ml.) a 10% citric acid solution, with (1×150 ml.) water, with (2×150 ml.) saturated solution of sodium bicarbonate and then with (2×100 ml.) water. The organic layer is dried with anhydrous magnesium sulfate and the solvent evaporated to yield carbobenzoxy-β-alanyl-L-proline t-butyl ester.

Source