Réaction #2122494

Équation de réaction

Acetyl chloride

methanol

4-hydroxy-1-methoxypiperidine-4-carbonitrile

methanol

→

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

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONAfter the addition
2. 2
   AutreThe cooling was removed
3. 3
   Autrethe suspension formed
4. 4
   workup.WAITwas left
5. 5
   workup.STIRRINGstirring at room temperature overnight
6. 6
   AutreThe 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
    Séchagedried over magnesium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated
13. 13
    AutreThe crude product was used without further purification

Mode opératoire

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