Acetaldehyde → Gramine

Temperature

0 °C

To a solution of indole (46.8 g, 0.40 mmol) in glacial AcOH (200 mL) at 0° C. under a nitrogen blanket was added isopropylamine (37.6 mL, 0.44 mol) over a period of 10 minutes. To a cold solution was added a solution of acetaldehyde (22.4 mL, 0.44 mL) in benzene (60 mL) over 30 minutes. The resulting brown solution was stirred at 0° C. for 24 hours, after which the reaction mixture was poured into 400 mL of ice water. The mixture was extracted with Et2O (3×200 mL). The combined ether extracts were extracted with 0.5 N HCl (3×150 mL) and the combined aqueous extracts were washed with Et2O (2×200 mL). The combined aqueous extracts were cooled to 0° C., then made basic with 50% aqueous NaOH to pH 12. The precipitate was extracted with CH2Cl2 (3×300 mL) and the combined extracts were washed with brine (200 mL), dried over Na2SO4, filtered, and the solvent was removed under reduced pressure to afford Intermediate 15 as a yellow semisolid (30 g, 37%): TLC Rf (1:1 CH2Cl2/EtOAc)=0.11.

1. extractionThe mixture was extracted with Et2O (3×200 mL)
2. extractionThe combined ether extracts were extracted with 0.5 N HCl (3×150 mL)
3. washthe combined aqueous extracts were washed with Et2O (2×200 mL)
4. temperatureThe combined aqueous extracts were cooled to 0° C.
5. extractionThe precipitate was extracted with CH2Cl2 (3×300 mL)
6. washthe combined extracts were washed with brine (200 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customthe solvent was removed under reduced pressure

ORD record

ord-9ce40ad975c5490d988a9f31f03c9def

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105506B2