Hydrochloric Acid → HCID 131720398, compound

Temperature

-10 °C

A solution of Cbz-Pro-OH (10.1 gm) in 2-propanol (IPA, 100 mL) was cooled to -5° C., and NMM (4.4 mL) was added with additional cooling to -10° C. iso-Butyl chloroformate (5.2 mL) was added dropwise while maintaining the temperature at -10° to -15° C. After the addition was complete, a solution of HCl.D-Ala-NH2 (5.0 gm) and NMM (4.4 mL) in water (50 mL) was added and the mixture was stirred at -10° C. for another 30 minutes. The cooling bath was then removed and the solution stirred another three hours. The reaction was quenched in a mixture of EtOAc (200 mL) and water (100 mL) containing NaHCO3 (5 gm) and NaCl (5 gm). The layers were separated and the aqueous layer extracted with EtOAc (2×100 mL). The organic layers were combined and washed with water (2×50 mL) and then concentrated in vacuo to dryness. The residue was taken up in EtOAc (250 mL) and the solution washed with water (2×50 mL) to remove any residual IPA. The organic solution was concentrated in vacuo to about 50 mL and treated with EtOAc (50 mL) and heptane (50 mL) and the product crystallized. The solids were filtered, washed on the filter with heptane and dried in vacuo to yield 8.2 gm Cbz-Pro-D-Ala-NH2. HPLC: 99.2 pa %, [α]D =-11.2 (CHCl3).

1. additionwas added dropwise
2. temperaturewhile maintaining the temperature at -10° to -15° C
3. additionAfter the addition
4. customThe cooling bath was then removed
5. stirringthe solution stirred another three hours
6. customThe reaction was quenched in a mixture of EtOAc (200 mL) and water (100 mL)
7. additioncontaining NaHCO3 (5 gm) and NaCl (5 gm)
8. customThe layers were separated
9. extractionthe aqueous layer extracted with EtOAc (2×100 mL)
10. washwashed with water (2×50 mL)
11. concentrationconcentrated in vacuo to dryness
12. washthe solution washed with water (2×50 mL)
13. customto remove any residual IPA
14. concentrationThe organic solution was concentrated in vacuo to about 50 mL
15. additiontreated with EtOAc (50 mL) and heptane (50 mL)
16. customthe product crystallized
17. filtrationThe solids were filtered
18. washwashed on the
19. filtrationfilter with heptane
20. customdried in vacuo

ORD record

ord-490a64f8111742b0813cf389fa13608a

Source dataset

uspto-grants-1998_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05710247