Dimethylformamide → 6-Phenethyl-octahydro-pyrrolo[2,3-c]pyridine

To a solution of 6 in dichloromethane (25 mL) is added sequentially diisopropylethylamine (4.17 mL, 24 mmol), t-Boc-L-cyclohexylglycine (1.54 g, 6 mmol), and a solution of 0.45 M HOBt/HBTU in DMF (16 mL, 7.19 mmol). The mixture is stirred overnight at room temperature, then diluted with EtOAc (200 mL) and washed sequentially with 1 M aq. citric acid (50 mL), water (50 mL), aq. Sat. NaHCO3 (50 mL) and brine (2×50 mL). The organic layer is dried and concentrated under vacuum. The residue is purified by flash chromatography (silica gel; Hexane/EtOAc 1:9) to provide a yellow oil. The yellow oil is dissolved in dichloromethane (20 mL), TFA (10 mL) is added and the mixture is stirred at room temperature for 3 h. The mixture is concentrated and the residue is dissolved in dichloromethane (100 mL) and neutralized with saturated sodium bicarbonate. The solution is extracted with dichloromethane (3×50 mL). The organic extracts are combined, dried and concentrated under vacuum to provide 1.75 g (79% two steps) of the title compound which is used in next step without further purification or characterization.

1. washwashed sequentially with 1 M aq. citric acid (50 mL), water (50 mL), aq. Sat. NaHCO3 (50 mL) and brine (2×50 mL)
2. customThe organic layer is dried
3. concentrationconcentrated under vacuum
4. customThe residue is purified by flash chromatography (silica gel; Hexane/EtOAc 1:9)
5. customto provide a yellow oil
6. stirringthe mixture is stirred at room temperature for 3 h
7. concentrationThe mixture is concentrated
8. dissolutionthe residue is dissolved in dichloromethane (100 mL)
9. extractionThe solution is extracted with dichloromethane (3×50 mL)
10. customdried
11. concentrationconcentrated under vacuum

ORD record

ord-5a1549ca631a414c972b06e832910179

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419975B2