Sodium cyanoborohydride → HCID 22609198, compound

NaCNBH3 (0.223 g, 3.54 mmol) was added to a solution of 10-(2,6-difluorophenyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.336 g, 1.13 mmol) in CF3CO2H (6 mL), which was cooled in an ice-water bath. After stirring for 4 h, the reaction mixture was quenched by adding 6N HCl (6 mL). The resulting mixture was refluxed for 0.45 h. The mixture was cooled and made basic by the addition of 6N NaOH (25 mL). The basic mixture was combined with CHCl3 (30 mL) and H2O (5 mL) and the layers were separated. The aqueous layer was extracted with CHCl3 (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product (0.78 g) was chromatographed (SiO2 35 g, eluted with 90:10:2 CH2Cl2:CH3OH:conc. NH4OH) to yield 10-(2,6-difluorophenyl)-1,2,3,4,5,5a,6,10b-octahydroazepino[4,5-b]indole (0.232 g) in 69% yield. 1H NMR (400 MHz, CD3OD) δ 1.37, 1.61, 1.94, 2.05, 2.44, 2.65-2.73, 3.05, 3.54, 4.19, 6.52, 6.63, 7.03-7.09, 7.41: MS (ESI+) for C18H18F2N2 m/z 301.2 (M+H)+.

1. temperaturewas cooled in an ice-water bath
2. customthe reaction mixture was quenched
3. additionby adding 6N HCl (6 mL)
4. temperatureThe resulting mixture was refluxed for 0.45 h
5. temperatureThe mixture was cooled
6. additionmade basic by the addition of 6N NaOH (25 mL)
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with CHCl3 (2×50 mL)
9. dry with materialThe combined organic layers were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product (0.78 g) was chromatographed
13. wash(SiO2 35 g, eluted with 90:10:2 CH2Cl2:CH3OH:conc. NH4OH)

ORD record

ord-c29cb328c39d4823b412035fd737b1fa

Source dataset

uspto-grants-2004_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06828314B2