Reaction #44013

Reaction equation

ketone

benzyl 2-ethyl-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate

SMe2

4-Chlorophenylmagnesium bromide

BF3.Et2O

NH4Cl

NH4OH

→

83

Yield 33.3%

benzyl 2-(4-chlorophenyl)-6-ethyl-4-oxopiperidine-1-carboxylate

Yield 33.3%

Solvents

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGAfter 2 hr stirring at −78° C.
2. 2
   TemperatureThe mixture was warmed to rt
3. 3
   Extractionextracted with EtOAc (200 mL×3)
4. 4
   WashThe combined organic layers were washed with brine
5. 5
   Otherdried
6. 6
   Concentrationconcentrated to a residue
7. 7
   Otherpurified by silica gel chromatography (0-40% EtOAc/hexanes)

Procedure

CuBr.SMe2 (5.6 g, 27.2 mmol) was added to dry THF (64 mL). It was cooled to −78° C. 4-Chlorophenylmagnesium bromide (27.2 mL, 1 M in THF, 27.2 mmol) was added to the mixture slowly over 1 hr at −78° C. Then BF3.Et2O (3.44 mL, 27.2 mmol) was added and the mixture was stirred for 5 min. Then ketone 82 (4 g, 8.1 mmol) in THF (55 mL) was added slowly over 1 hr at −78° C. After 2 hr stirring at −78° C., an aqueous solution of NH4Cl/conc. NH4OH (1:1, 20%, 60 mL) was added. The mixture was warmed to rt and extracted with EtOAc (200 mL×3), The combined organic layers were washed with brine, dried and concentrated to a residue and purified by silica gel chromatography (0-40% EtOAc/hexanes) to afford pure 83 (1 g, 2.7 mmol, 33%) as a mixture of cis stereoisomers.

Source