Reaction #640602

Reaction equation

2-chlorohydroxyiminoacetic acid ethyl ester

1-(4-pyrrolidin-1-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone

triethylamine

→

5-acetyl-7a-pyrrolidin-1-yl-3a,4,5,6,7,7a-hexahydro-isoxazolo[4,5-c]pyridine-3-carboxylic acid ethyl ester

Solvents

DCM

DCM

Conditions

Workup

1. 1
   Temperaturethe solution warmed up
2. 2
   workup.ADDITIONwere slowly added dropwise
3. 3
   workup.STIRRINGThe mixture was stirred for 12 h at RT
4. 4
   Washwashed, firstly with 10% (weight percent) citric acid solution in water
5. 5
   OtherAfter removal of the solvent under a vacuum
6. 6
   Otherthe residue was purified by column chromatography (SiO2, EtOAc/EtOH 9:1)

Procedure

A solution of 17.9 g (0.118 mol) of 2-chlorohydroxyiminoacetic acid ethyl ester in 20 mL of DCM was added to a solution of 16.3 g (84 mmol) of 1-(4-pyrrolidin-1-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone (A) in 150 mL of DCM. On so doing, the solution warmed up and turned red. After cooling to 0° C. (ice bath), 16.4 g (0.118 mol) of triethylamine were slowly added dropwise with stirring. The mixture was stirred for 12 h at RT and then washed, firstly with 10% (weight percent) citric acid solution in water, and then with sat. aq. common salt solution. After removal of the solvent under a vacuum, the residue was purified by column chromatography (SiO2, EtOAc/EtOH 9:1). 18.5 g (71% of theoretical) of the desired product 5-acetyl-7a-pyrrolidin-1-yl-3a,4,5,6,7,7a-hexahydro-isoxazolo[4,5-c]pyridine-3-carboxylic acid ethyl ester (B) were obtained in the form of a brown oil.

Source