Reaction #2122494

Reaction equation

Acetyl chloride

methanol

4-hydroxy-1-methoxypiperidine-4-carbonitrile

methanol

→

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

Conditions

Workup

1. 1
   workup.ADDITIONAfter the addition
2. 2
   OtherThe cooling was removed
3. 3
   Otherthe suspension formed
4. 4
   workup.WAITwas left
5. 5
   workup.STIRRINGstirring at room temperature overnight
6. 6
   OtherThe solvent was evaporated under vacuum
7. 7
   workup.DISSOLUTIONthe residue was dissolved in cold (0° C.) water
8. 8
   workup.ADDITIONNaHCO3 (saturated aqueous solution) was added carefully
9. 9
   ExtractionThe aqueous phase was thoroughly extracted three times with ethyl acetate
10. 10
    Dryingdried over magnesium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    OtherThe crude product was used without further purification

Procedure

Acetyl chloride (40.7 g, 0.52 mol) was added slowly to dry methanol (115 ml) cooled to 0° C. under argon. After the addition, the solution was stirred for an additional ½ hour at 0° C. This solution was then added dropwise into a cold (0° C.) solution of 4-hydroxy-1-methoxypiperidine-4-carbonitrile (5.40 g, 34.6 mmol) in methanol (45 ml). The cooling was removed and the suspension formed was left stirring at room temperature overnight. The solvent was evaporated under vacuum and the residue was dissolved in cold (0° C.) water. NaHCO3 (saturated aqueous solution) was added carefully to adjust the pH to 7. The aqueous phase was thoroughly extracted three times with ethyl acetate. The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The crude product was used without further purification. Yield: 4.9 g of 4-hydroxy-1-methoxy-piperidine-4-carboxylic acid methyl ester (title compound P4.4) as light yellow oil.

Source