Hydrochloric Acid → 5-Chloro-1,2,3,4-tetrahydroquinoline

Temperature

60 °C

Based on B. S. Rauckman et al., J. Med. Chem., 1989, 32, 1927-1935, 5-chloroquinoline (1.01 g, 6.2 mmol) was dissolved into anh. EtOH (30 mL) under N2 at RT. Concentrated HCl (2.14 mL, 24.8 mmol) was added, followed by the addition of the NaCNBH3 (1.56 g, 24.8 mmol). This produced a vigorous gas and heat evolution. The reaction was heated to 60° C. for 2 h, then cooled and stirred at RT for an additional 18 h. The reaction was quenched by adjusting the pH to approximately 9 with 2 N NaOH. This mixture was extracted 3 times with EtOAc. The EtOAc extracts were washed brine, combined, dried over Na2SO4, filtered, and concentrated, then eluted through a 17×2.5 cm column of silica gel (5%, 10%, 15%, 40% and 50% EtOAc/Hexane step gradient) giving 5-chloro-1,2,3,4-tetrahydroquinoline as a green oil: MS m/z 168=[M+H]+. Calc'd for C9H10NCl—167.05.

1. customThis produced a vigorous gas
2. temperatureheat evolution
3. temperaturecooled
4. customThe reaction was quenched
5. extractionThis mixture was extracted 3 times with EtOAc
6. washThe EtOAc extracts were washed brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. washeluted through a 17×2.5 cm column of silica gel (5%, 10%, 15%, 40% and 50% EtOAc/Hexane step gradient)

ORD record

ord-d2ef94b318cf432382b6fc095f467a9b

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06881737B2