Hydrochloric Acid → 7-Chloro-1,2,3,4-tetrahydroquinoline

HRID 1815923Notes

Reaction equation

HRID 1815923 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.Cl.[BH3-]C#N.[Na+]>CCO>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([CH2:2][CH2:3][CH2:4][NH:5]2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 68664,7-DichloroquinolineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 130473667-Chloro-1,2,3,4-tetrahydroquinoline

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

Similar to the process reported by B. S. Rauckman, et. al., J. Med. Chemn., 1989, 32, 1927-1935, 4,7-dichloroquinoline (1.02 g, 5.1 mmol) was dissolved into anh. EtOH (30 mL) under N2 at RT. Concentrated HCl (1.76 mL, 20.4 mmol) was added, followed by the addition of the NaCNBH3 (1.28 g, 20.4 mmol). This produced 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 30×2.5 cm column of silica gel (3.75% EtOAc/Hexane) giving 7-chloro-1,2,3,4-tetrahydro-quinoline as an orange solid: MS m/z 168=[M+H]+. Calc'd for C9H10ClN: 167.05.

Workup

  1. temperatureThis produced vigorous gas and heat evolution
  2. temperaturecooled
  3. customThe reaction was quenched
  4. extractionThis mixture was extracted 3 times with EtOAc
  5. washThe EtOAC extracts were washed brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluted through a 30×2.5 cm column of silica gel (3.75% EtOAc/Hexane)

Sources & evidence

ORD record
ord-1f0154be65cf463584acd26813fa2f6b
Source dataset
uspto-grants-2005_04
Patent number
US06881737B2

Reaction notes

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