Reaction #72092

Reaction equation

hydrochloric acid

Sodium methoxide

Methyl acetoacetate

benzyl cis(±)-[1-(chloroacetyl)-3-methoxypiperidin-4-yl]carbamate

Benzyl cis(±)-[1-(chloroacetyl)-3-methoxypiperidin-4-yl]carbamate

→

title compound

Methyl cis(±)-2-acetyl-4-(4-{[(benzyloxy)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-oxobutanoate

Solvents

ethyl acetate

methanol

methanol

Conditions

Workup

1. 1
   workup.ADDITIONThe solution was added to the reaction solution
2. 2
   workup.STIRRINGthe mixture was stirred at 70° C. overnight
3. 3
   Washwashed with brine
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   Concentrationconcentration under reduced pressure

Procedure

Methyl acetoacetate (510 mg, 4.4 mmol) was dissolved in methanol (15 ml). Sodium methoxide (210 mg, 3.9 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Further, benzyl cis(±)-[1-(chloroacetyl)-3-methoxypiperidin-4-yl]carbamate obtained in Example (188a) was dissolved in methanol (10 ml). The solution was added to the reaction solution, and the mixture was stirred at 70° C. overnight. The reaction solution was diluted with ethyl acetate, neutralized with 1 N hydrochloric acid, washed with brine, and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the title compound was obtained. The resulting compound was used for the next reaction without purification.

Source