Diethyl Ether → N-(4-chlorophenyl)-1-methylpiperidin-4-amine

To a solution of 4-chloroaniline (4.59 g, 30×1.2 mmol) and 1-methyl-4-piperidone (3.39 g, 30 mmol) in benzene (12 ml) is added Molecular Sieve 4A (6 g), and the resultant mixture is heated under reflux over a period of 20 hours. After cooling, the reaction mixture is mixed with ether and filtered to remove the Molecular Sieve. The filtrate is concentrated in vacuo, and the residue is dissolved in 95% ethanol (50 ml). Sodium borohydride (0.6 g, 15 mmol) is added to the solution, which is stirred at room temperature over a period of 5 hours. The reaction mixture is mixed with water and the ethanol is evaporated therefrom. The aqueous residue is shaken with methylene chloride, and the methylene chloride layer is dried over anhydrous potassium carbonate and concentrated in vacuo. The residue is distilled to give crude product (5.89 g) b.p. 130°-150° C./1 mmHg. This substance is recrystallized from ether-petroleum ether to give 4 -(4-chloroanilino)-1-methylpiperidine (5.25 g) as crystals melting at 91° to 92° C. The yield is 78%.

1. temperatureunder reflux over a period of 20 hours
2. temperatureAfter cooling
3. filtrationfiltered
4. customto remove the Molecular Sieve
5. concentrationThe filtrate is concentrated in vacuo
6. dissolutionthe residue is dissolved in 95% ethanol (50 ml)
7. customthe ethanol is evaporated
8. stirringThe aqueous residue is shaken with methylene chloride
9. dry with materialthe methylene chloride layer is dried over anhydrous potassium carbonate
10. concentrationconcentrated in vacuo
11. distillationThe residue is distilled
12. customto give crude product (5.89 g) b.p. 130°-150° C./1 mmHg
13. customThis substance is recrystallized from ether-petroleum ether

ORD record

ord-31cea8fede91452688ea5228cd231b8f

Source dataset

uspto-grants-1985_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04560684