2-Phenylpropionic acid → HCID 18611253, compound

Phenylpropionic acid (3 g, 20 m mole) was dissolved in 1,2-dichloroethane (80 ml), and while maintaining the solution at an internal temperature between 5 and 8° C., L-alanyl-L-prolyl-L-proline methyl ester hydrochloride (6.69g), triethyl amine (2.02 g, 20 m mole), 1-hydroxybenzotriazole (0.35 g, 3 m mole), and dicyclohexylcarbod iimide (4.12 g, 20 m mole) were added, and the thus obtained mixture was stirred for 4 hours. After that, it was stirred at room temperature overnight, and the precipitated dicyclohexyl urea crystals and triethyl amine hydrochloride crystals were filtered off and were washed with 1,2-dichloroethane (20 ml). The filtrate and the washing were mixed together, and the obtained mixture was washed with 0.5N hydrochloric acid (50 ml), water (80 ml), 0.5N aqueous sodium hydroxide (60 ml) and water (80 ml) in order, and the 1,2-dichloroethane phase was concentrated under reduced pressure To the obtained syrupy residue, water (50 ml) and 5N aqueous sodium hydroxide (5 ml) were added and the obtained mixture was stirred at room temperature for 2 hours. After completion of the saponification, the precipitated dicyclohexyl urea crystals were filtered off and washed with water (5 ml). The filtrate and the washings were mixed together, and the thus obtained mixture was adjusted to pH 2.5 with 6N hydrochloric acid and was extracted with 1,2-dichloroethane (100 ml). The 1,2-dichloroethane phase was washed with water (30 ml), and the 1,2-dichloroethane was distilled off therefrom under reduced pressure To the concentrated residue, carbon tetrachloride (30 ml) was added, and the obtained solution was concentrated under reduced pressure and ethyl ether (100 ml) was added thereto. The solution was changed slowly to a solid material while stirring. A solid material was obtained by filtration, and dried to obtain N-(3-phenylpropionyl)-L-alanyl-L-prolyl-L-proline (5.8 g).

1. additionwere added
2. stirringAfter that, it was stirred at room temperature overnight
3. filtrationthe precipitated dicyclohexyl urea crystals and triethyl amine hydrochloride crystals were filtered off
4. washwere washed with 1,2-dichloroethane (20 ml)
5. additionThe filtrate and the washing were mixed together
6. washthe obtained mixture was washed with 0.5N hydrochloric acid (50 ml), water (80 ml), 0.5N aqueous sodium hydroxide (60 ml) and water (80 ml) in order
7. concentrationthe 1,2-dichloroethane phase was concentrated under reduced pressure To the obtained syrupy residue, water (50 ml) and 5N aqueous sodium hydroxide (5 ml)
8. additionwere added
9. stirringthe obtained mixture was stirred at room temperature for 2 hours
10. filtrationAfter completion of the saponification, the precipitated dicyclohexyl urea crystals were filtered off
11. washwashed with water (5 ml)
12. additionThe filtrate and the washings were mixed together
13. extractionwas extracted with 1,2-dichloroethane (100 ml)
14. washThe 1,2-dichloroethane phase was washed with water (30 ml)
15. distillationthe 1,2-dichloroethane was distilled off
16. additionunder reduced pressure To the concentrated residue, carbon tetrachloride (30 ml) was added
17. concentrationthe obtained solution was concentrated under reduced pressure and ethyl ether (100 ml)
18. additionwas added
19. stirringwhile stirring
20. customA solid material was obtained by filtration
21. customdried

ORD record

ord-c2c9475217da4a8b9864bab69f967a12

Source dataset

uspto-grants-1988_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04719200