Sodium Chloride → rac-5-{[2-(5-Fluoro-2-methoxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carbonitrile

HRID 875327Notes

Reaction equation

HRID 875327 reaction equation
O=[C:2]1[CH2:11][CH2:10][CH2:9][C:8]2[N:7]=[C:6]([C:12]#[N:13])[CH:5]=[CH:4][C:3]1=2.[F:14][C:15]1[CH:16]=[CH:17][C:18]([O:24][CH3:25])=[C:19]([CH2:21][CH2:22][NH2:23])[CH:20]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+].[Cl-].[Na+]>C1(C)C=CC=CC=1.O>[F:14][C:15]1[CH:16]=[CH:17][C:18]([O:24][CH3:25])=[C:19]([CH2:21][CH2:22][NH:23][CH:2]2[CH2:11][CH2:10][CH2:9][C:8]3[N:7]=[C:6]([C:12]#[N:13])[CH:5]=[CH:4][C:3]2=3)[CH:20]=1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 4311764Sodium borohydrideHCID 220150102-(5-Fluoro-2-methoxyphenyl)ethan-1-amineHCID 867098005-Oxo-5,6,7,8-tetrahydroquinoline-2-carbonitrile

Product 1

HCID 89940804rac-5-{[2-(5-Fluoro-2-methoxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

21.98 g (127.66 mmol) of 5-oxo-5,6,7,8-tetrahydroquinoline-2-carbonitrile, 21.6 g (127.66 mmol) of 2-(5-fluoro-2-methoxyphenyl)ethanamine [CAS Reg.-No. 1000533-03-8] and 3.64 g (19.15 mmol) of p-toluenesulphonic acid monohydrate were dissolved in 511 ml of toluene, and the solution was stirred under reflux overnight using a water separator. 200 ml of toluene were then distilled off and, after cooling, replaced by fresh toluene. The reaction solution was then evaporated to dryness and the resulting residue was taken up in 511 ml of anhydrous ethanol and 511 ml of anhydrous THF. With stirring at a temperature of from 15° to 20° C., 9.66 g (255.32 mmol) of sodium borohydride were added a little at a time to the solution (careful: reaction mixture foams). The reaction solution was then stirred at the same temperature overnight. 10% strength aqueous sodium chloride solution was then added carefully, and the reaction mixture was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulphate, filtered and then concentrated to dryness. The residue obtained in this manner was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1). This gave 19.5 g (59.93 mmol, 46% of theory) of the target compound.

Workup

  1. temperatureunder reflux overnight
  2. distillation200 ml of toluene were then distilled off
  3. temperatureafter cooling
  4. customThe reaction solution was then evaporated to dryness
  5. additionwere added a little at a time
  6. customto the solution (careful: reaction mixture foams)
  7. stirringThe reaction solution was then stirred at the same temperature overnight
  8. extractionthe reaction mixture was extracted twice with ethyl acetate
  9. dry with materialThe combined organic phases were dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue obtained in this manner
  13. customwas purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-5306e23728d74f72bc2f70b0bfb23c48
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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