Hydrochloric Acid → HCID 21283631, compound

HRID 2232556Notes

Reaction equation

HRID 2232556 reaction equation
[C:1]1([C:7]2[CH:16]=[C:15]([CH2:17][CH2:18][C:19](O)=[O:20])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OC(Cl)=O)C.Cl.[CH3:29][NH:30][CH:31]([CH2:33][CH3:34])[CH3:32].Cl>C(Cl)(Cl)Cl.CC(C)=O.C(OCC)C.C(N(CC)CC)C>[CH3:29][N:30]([CH:31]([CH3:32])[CH2:33][CH3:34])[C:19](=[O:20])[CH2:18][CH2:17][C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:16]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10928Ethyl chloroformateHCID 21273362N-Methylbutan-2-amine--hydrogen chloride (1/1)HCID 21283615HCID 21283615, compound

Product 1

HCID 21283631HCID 21283631, compoundYield 15.3%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

Triethylamine (3.78 cc) is added to a suspension of 2-phenyl-4-quinolinepropanoic acid (2.5 g) in chloroform (100 cc), followed, under nitrogen and after the mixture has been cooled to 10° C., by ethylchloroformate (1.24 g). The mixture is then stirred for 40 minutes at room temperature (approximately 20° C.), and N-methyl-2-butanamine hydrochloride (1.05 g) is then introduced in small portions. The mixture is stirred for 20 hours at room temperature (approximately 20° C.). After evaporation of the solvent under reduced pressure, the residue is taken up in ethyl acetate, and the organic phase is washed with saturated aqueous sodium carbonate solution and dried over magnesium sulphate. The residue obtained after evaporation of the solvent under reduced pressure is chromatographed under pressure on silica gel, initially with a cyclohexane/toluene/diethylamine (80:15:5 by volume) mixture, a second time with a cyclohexane/toluene/diethylamine (90:7.5:2.5 by volume) mixture, and a third time with a hexane/ethyl acetate (50:50 by volume) mixture. The residue obtained is taken up in acetone and, after addition of a solution of hydrochloric acid in ethyl ether, the product is isolated in the form of the crude hydrochloride. The latter is recrystallized in an isopropanol/isopropyl ether mixture. After a return to the base using 2N sodium hydroxide, extraction with ethyl acetate and evaporation under reduced pressure, N-methyl-N-(1-methylpropyl)-2-phenyl-4-quinolinepropanamide (0.45 g) is isolated in the form of an oil, the proton NMR spectrum of which in deuterated chloroform shows the following characteristics:

Workup

  1. additionis then introduced in small portions
  2. customAfter evaporation of the solvent under reduced pressure
  3. washthe organic phase is washed with saturated aqueous sodium carbonate solution
  4. dry with materialdried over magnesium sulphate
  5. customThe residue obtained
  6. customafter evaporation of the solvent under reduced pressure
  7. customis chromatographed under pressure on silica gel, initially with a cyclohexane/toluene/diethylamine (80:15:5 by volume) mixture
  8. customThe residue obtained
  9. customthe product is isolated in the form of the crude hydrochloride
  10. customThe latter is recrystallized in an isopropanol/isopropyl ether mixture
  11. extraction2N sodium hydroxide, extraction
  12. customwith ethyl acetate and evaporation under reduced pressure

Sources & evidence

ORD record
ord-576281f0efd446f8bfb57fc38e60e008
Source dataset
uspto-grants-1988_11
Patent number
US04788204

Reaction notes

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