Reaction #2122485

Reaction equation

(2,4,6-trimethylphenyl)-acetyl chloride

4-hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester

4-dimethylaminopyridine DMAP

→

1-methoxy-4-[2-(2,4,6-trimethyl-phenyl)-acetoxy]-piperidine-4-carboxylic acid ethyl ester

Solvents

pyridine

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was warmed up to room temperature
2. 2
   workup.WAITleft
3. 3
   ConcentrationThen the reaction mixture was concentrated
4. 4
   workup.ADDITIONcold (0° C.) water was added
5. 5
   ExtractionThe aqueous phase was thoroughly extracted three times with dichloromethane
6. 6
   Washwashed with brine
7. 7
   Dryingdried over sodium sulfate
8. 8
   Concentrationconcentrated
9. 9
   OtherThe crude product was purified by column chromatography on silica gel (ethyl acetate/cyclohexane 1:4)

Procedure

To a solution of 4-hydroxy-1-methoxy-piperidine-4-carboxylic acid ethyl ester (0.5 g, 2.46 mmol) in 15 ml pyridine under argon was added 4-dimethylaminopyridine DMAP (0.11 g, 0.9 mmol). The solution was cooled down to 0° C., then (2,4,6-trimethylphenyl)-acetyl chloride (0.58 g, 2.95 mmol) was added dropwise. The reaction mixture was warmed up to room temperature and left stirring for 3 days. Then the reaction mixture was concentrated and cold (0° C.) water was added. The aqueous phase was thoroughly extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography on silica gel (ethyl acetate/cyclohexane 1:4) to give pure 1-methoxy-4-[2-(2,4,6-trimethyl-phenyl)-acetoxy]-piperidine-4-carboxylic acid ethyl ester (compound P3.6) as light yellow oil. Yield: 610 mg.

Source