Pyridine → HCID 59003172, compound

Add phosgene (1.5 mmol, 1.93 M solution in toluene) to a solution of cyclopentanol (0.17 g, 1.9 mmol) in DCM (3 mL) at 0° C. under nitrogen. To this cooled solution add diisopropyl ethylamine (0.26 mL, 1.5 mmol) dropwise. After stirring for 1 h with cooling, warm the mixture to room temperature and add 7-Methyl-8-trifluoromethoxy-1,2,3,4-tetrahydro-benzo[b]azepin-5-one (0.10 g, 0.38 mmol) in dichloromethane (2 mL). After stirring for 1 h at room temperature, dilute with dichloromethane (5 mL) and wash with 5% HCl (5 mL) followed by water (5 mL) and brine (5 mL). Dry the organics over sodium sulfate, filter, and remove solvent under vacuum. To this residue, add titanium isopropoxide (1 mL) and 3,5-bis(trifluoromethyl)benzylamine (0.18 g, 0.76 mmol). After stirring at room temperature over night dilute with methanol (3 mL) and add sodium borohydride (3.0 mmol). After 1 h of stirring at room temperature dilute the reaction with water (5 mL) and ethyl acetate (10 mL). Filter the resulting emulsion through a pad of celite and rinse with ethyl acetate (3×5 mL). Separate the organics and wash with water (10 mL) followed by brine (10 mL). Dry the organics over sodium sulfate, filter, and concentrate under vacuum. To This residue in dichloromethane (5 mL), add acetyl chloride (2.3 mmol) followed by pyridine (2.3 mmol). After stirring for 0.5 h dilute with dichloromethane (5 mL), wash with 5% HCl (5 mL), water (5 mL) and brine (5 mL). Dry the organics over sodium sulfate and concentrate under vacuum. Chromatograph the crude product over silica gel using ethyl acetate/hexane (10-30%) to elute. This provides the title compound (0.14 g, 60%) as an oil that solidifies upon standing: MS (ES+): 641 (M+H).

1. temperaturewith cooling
2. stirringAfter stirring for 1 h at room temperature
3. washwash with 5% HCl (5 mL)
4. dry with materialDry the organics over sodium sulfate
5. filtrationfilter
6. customremove solvent under vacuum
7. stirringAfter stirring at room temperature over night
8. stirringAfter 1 h of stirring at room temperature
9. additiondilute
10. filtrationFilter the resulting emulsion through a pad of celite
11. washrinse with ethyl acetate (3×5 mL)
12. customSeparate the organics and
13. washwash with water (10 mL)
14. dry with materialDry the organics over sodium sulfate
15. filtrationfilter
16. concentrationconcentrate under vacuum
17. stirringAfter stirring for 0.5 h
18. washwash with 5% HCl (5 mL), water (5 mL) and brine (5 mL)
19. dry with materialDry the organics over sodium sulfate
20. concentrationconcentrate under vacuum
21. washto elute

ORD record

ord-2f45bfb43da54696ac10f6fc98e2c13b

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749992B2