Hydrochloric Acid → 3-[Benzyl(methyl)amino]-1-(3-methoxyphenyl)-2-methylpropan-1-one

HRID 1631841Notes

Reaction equation

HRID 1631841 reaction equation
[CH2:1]=O.[C:3](#[N:5])C.[CH2:6](CN)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Cl.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([C:24](=[O:27])[CH2:25][CH3:26])[CH:21]=[CH:22][CH:23]=1>>[CH2:6]([N:5]([CH3:3])[CH2:26][CH:25]([CH3:1])[C:24]([C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([O:17][CH3:16])[CH:19]=1)=[O:27])[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 1001PhenethylamineHCID 6342AcetonitrileHCID 5847653'-Methoxypropiophenone

Product 1

HCID 665707103-[Benzyl(methyl)amino]-1-(3-methoxyphenyl)-2-methylpropan-1-one

Conditions

Temperature
65 °C

Procedure

In a four-neck 1 L flask equipped with reflux, thermometer and mechanical stirrer, the following are loaded: 95% w/w paraformaldehyde (19.2 g, 0.638 moles) and acetonitrile (300 mL/234 g, 5.70 moles). The mixture is cooled to a temperature less than 10° C., then the following are loaded: 97% w/w N-benzylmethylamine (77.3 g, 0.638 moles), 36% HCl (70.9 g/60.0 mL, 0.70 moles). Finally, 99.7% 1-(3-methoxy-phenyl)-propan-1-one (100 g, 0.608 moles) is added. The reaction mixture is heated at 65±5° C. for 20-24 hours and the conversion is verified by means of HPLC. Upon completed reaction, the solution is concentrated under vacuum at 35-50° C. and 200-300 mL of solvent is collected. Added to the mixture are: toluene (100 ml) and purified water (200 ml), and stirring proceeds for 30 minutes at ambient temperature. The phases are separated and toluene (200 ml) is added to the aqueous phase. The pH is brought to 11-13 with 28% NaOH (about 105 g). The mixture is stirred for 30 minutes and the phases separated. The toluene phase is distilled under vacuum at 35-45° C. IPA (100 mL) is then added and the residue solvent is distilled.

Workup

  1. customIn a four-neck 1 L flask equipped
  2. temperaturewith reflux
  3. customthermometer and mechanical stirrer, the following are loaded
  4. temperatureThe mixture is cooled to a temperature less than 10° C.
  5. customreaction
  6. concentrationthe solution is concentrated under vacuum at 35-50° C.
  7. custom200-300 mL of solvent is collected
  8. additionAdded to the mixture
  9. customtoluene (100 ml) and purified water (200 ml)
  10. customThe phases are separated
  11. additiontoluene (200 ml) is added to the aqueous phase
  12. stirringThe mixture is stirred for 30 minutes
  13. customthe phases separated
  14. distillationThe toluene phase is distilled under vacuum at 35-45° C
  15. additionIPA (100 mL) is then added
  16. distillationthe residue solvent is distilled

Sources & evidence

ORD record
ord-ee77b26b613841738d0df38835338b9a
Source dataset
uspto-grants-2014_07
Patent number
US08791287B2

Reaction notes

Loading…