Benzaldehyde → (S)-1-[2-Benzylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidine Hydrochloride

Methanolic hydrogen chloride (4M, 2 mL) was added to a solution of (S)-1-[2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]-4-(2-keto-1-benzimidazolinyl)piperidine (298 mg, 0.53 mmol) in methanol (2 mL) and the mixture was stirred at room temperature for 5 h. The solvent was evaporated under reduced pressure, dichloromethane (5 mL), triethylamine (0.148 mL, 107 mg, 1.06 mmol), benzaldehyde (0.065 mL, 67 mg, 0.64 mmol) and magnesium sulfate (300 mg) were added. The mixture was stirred at room temperature for 4 h., filtered and the solvent was evaporated under reduced pressure. Methanol (5 mL) was added, the mixture was cooled to 0° C. and sodium borohydride (40 mg, 1.06 mmol) was added. The mixture was stirred at room temperature for 1 h., aqueous sodium hydrogen carbonate (saturated, 20 mL) and water (10 mL) were added and the mixture was extracted with dichloromethane (3×20 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (99:1:0.1 increasing to 95:5:0.5). The residue was dissolved in methanol (5 mL), cooled to 0° C. and methanolic hydrogen chloride (1M, 0.44 mL) was added. The solvent was evaporated under reduced pressure and the residue was triturated with ether (5 mL). The solid was collected and dried in vacuo to give the title compound as a colorless solid (212 mg, 68%), m.p. 148°-151° C. Found: C, 57.18; H, 5.29; N, 9.27. C29H30Cl2N4O3.HCl.H2O requires: C, 57.29; H, 5.47; N, 9.22%. m/e (ES+) 553 (MH+).

1. additionwere added
2. stirringThe mixture was stirred at room temperature for 4 h.
3. filtrationfiltered
4. customthe solvent was evaporated under reduced pressure
5. additionMethanol (5 mL) was added
6. temperaturethe mixture was cooled to 0° C.
7. stirringThe mixture was stirred at room temperature for 1 h.
8. extractionthe mixture was extracted with dichloromethane (3×20 mL)
9. dry with materialThe combined organic fractions were dried (MgSO4)
10. customthe solvent was evaporated under reduced pressure
11. customThe residue was purified by flash column chromatography on silica gel
12. washeluting with CH2Cl2 /MeOH/NH3 (Aq.) (99:1:0.1 increasing to 95:5:0.5)
13. dissolutionThe residue was dissolved in methanol (5 mL)
14. temperaturecooled to 0° C.
15. additionmethanolic hydrogen chloride (1M, 0.44 mL) was added
16. customThe solvent was evaporated under reduced pressure
17. customthe residue was triturated with ether (5 mL)
18. customThe solid was collected
19. customdried in vacuo

ORD record

ord-94ae27c5a7e8409cba99d42b55871b77

Source dataset

uspto-grants-1999_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05885999