Reaction #657288

Reaction equation

HCl

1-methoxy-4-methylamino-piperidine-4-carboxylic acid methyl ester

(2,5-dimethyl-phenyl)-acetyl chloride

→

4-{[2-(2,5-dimethyl-phenyl)-acetyl]-methyl-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Solvents

ethyl acetate

pyridine

Conditions

Workup

1. 1
   workup.ADDITIONpoured on ice water
2. 2
   OtherThe layers were separated
3. 3
   Extractionthe aqueous phase extracted with ethyl acetate (3×25 ml)
4. 4
   Washthe combined organic phases washed with water (3×15 ml) and brine
5. 5
   Dryingdried over sodium sulfate
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1)

Procedure

To a solution of 1-methoxy-4-methylamino-piperidine-4-carboxylic acid methyl ester (200 mg, 0.99 mmol) in pyridine (5 ml) was added (2,5-dimethyl-phenyl)-acetyl chloride (240 mg, 1.31 mmol) dropwise at 0° C. The reaction mixture was stirred at 0° C. for one hour and at room temperature for 6 hours, poured on ice water, acidified to pH 7 with an aqueous 2N HCl solution and diluted with ethyl acetate (50 ml). The layers were separated, the aqueous phase extracted with ethyl acetate (3×25 ml), the combined organic phases washed with water (3×15 ml) and brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1). Yield: 170 mg of 4-{[2-(2,5-dimethyl-phenyl)-acetyl]-methyl-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (title compound P4.46) as a colorless gum.

Source