4-Methylmorpholine → carbobenzoxy-beta-alanyl-L-proline t-butyl ester

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.

1. customthe resulting reaction mixture
2. stirringis stirred
3. stirringis thereafter stirred overnight
4. customThe solvent of the reaction mixture is evaporated in vacuo at 30°-35°
5. dissolutionThe residue is dissolved in 800 ml
6. washof ethyl acetate which is washed with (2×150 ml.) a 10% citric acid solution
7. dry with materialThe organic layer is dried with anhydrous magnesium sulfate
8. customthe solvent evaporated

ORD record

ord-c7cd6af73aca49feafad7a587907044d

Source dataset

uspto-grants-1980_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04221706