Reaction #2122484

Reaction equation

water

4-dimethylaminopyridine DMAP

4-hydroxy-1-methoxy-piperidine-4-carbonitrile

(2,4,6-trimethyl-phenyl)-acetyl chloride

→

(2,4,6-trimethyl-phenyl)-acetic acid 4-cyano-1-methoxy-piperidin-4-yl ester

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   workup.WAIT30 minutes at 0° C. and finally left
3. 3
   workup.STIRRINGstirring overnight at room temperature
4. 4
   Extractionextracted three times with dichloromethane
5. 5
   DryingThe combined organic layers were dried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under vacuum
8. 8
   OtherThe crude product was purified by column chromatography on silica gel

Procedure

To a cooled (−20° C.) solution of 4-hydroxy-1-methoxy-piperidine-4-carbonitrile (0.32 g, 2.05 mmol) in 2 ml dichloromethane was added 4-dimethylaminopyridine DMAP (13 mg, 0.05 mmol) under argon. Then (2,4,6-trimethyl-phenyl)-acetyl chloride (0.52 g, 2.64 mmol) dissolved in dichloromethane (3 ml) was added dropwise. The reaction mixture was stirred at −20° C. for 30 minutes, then 30 minutes at 0° C. and finally left stirring overnight at room temperature. The reaction mixture was poured into water and extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated under vacuum. The crude product was purified by column chromatography on silica gel to give pure (2,4,6-trimethyl-phenyl)-acetic acid 4-cyano-1-methoxy-piperidin-4-yl ester (compound P3.5) as white solid, mp 75-78° C. Yield: 480 mg.

Source