Reaction #44007

Reaction equation

NH4Cl

Boron trifluoride dimethyl etherate

NH4OH

compound 66

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

4-Chlorophenylmagnesium bromide

→

product 67

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

Solvents

THF

THF

EtOAc

Conditions

Workup

1. 1
   Otherproduced an orange then green-like suspension
2. 2
   workup.STIRRINGstirred for 5 minutes
3. 3
   workup.STIRRINGAfter stirring 2 hours at −78° C.
4. 4
   Temperatureto warm-up to room temperature
5. 5
   Extractionto extract (3×100 mL)
6. 6
   Washthe combined organic layers were washed with brine
7. 7
   Dryingdried (MgSO4)
8. 8
   OtherSolvent was removed by rotary evaporation
9. 9
   Otherthe residue was purified by flash chromatography

Procedure

CuBr.SMe2 complex (1.49 g, 7.26 mmol) was added to 25 mL of anhydrous THF and cooled to −78° C. 4-Chlorophenylmagnesium bromide (7.26 mL, 1.0 M in THF, 7.26 mmol) was added slowly via syringe. Stirring at −78° C. for 1 hour produced an orange then green-like suspension. Boron trifluoride dimethyl etherate (0.92 mL, 7.26 mmol) was added and stirred for 5 minutes. To the newly formed complex was then added over 1 hour a solution of the compound 66 (1.0 g, 4.32 mmol) in 15 mL of anhydrous THF. After stirring 2 hours at −78° C., 16 mL of aq. 20% NH4Cl/conc. NH4OH (1:1) was added, and the mixture was allowed to warm-up to room temperature. EtOAc was used to extract (3×100 mL) and the combined organic layers were washed with brine and dried (MgSO4). Solvent was removed by rotary evaporation and the residue was purified by flash chromatography to give the product 67 as a colorless oil.

Source