Reaction #1121793

Reaction equation

bromopropionaldehyde dimethyl acetal

( 1 )

4-Bromo-pyridine-2-carboxylic acid methoxy-methyl-amide

→

1-(4-Bromo-pyridin-2-yl)-4,4-dimethoxy-butan-1-one

Solvents

THF

water

dry ice

THF

Conditions

Workup

1. 1
   Dryingdried round bottom flask at −70° C. (acetone-dry ice bath)
2. 2
   workup.ADDITIONis slowly added the Grignard reagent
3. 3
   Temperaturemaintaining internal temperature around −68° C. to −70° C
4. 4
   Otherremoved
5. 5
   workup.ADDITIONThe mixture is poured into a separatory funnel
6. 6
   Extractionthe mixture is extracted 3 times with ethyl acetate (150 mL)
7. 7
   Dryingdried over Na2SO4
8. 8
   Otherthe solvent evaporated
9. 9
   Otherleaving a thick yellow oil (11 g, 100% crude yield, MS ES+258.02)

Procedure

To a solution of (1) (8.86 g, 36.2 mmole) in 250 mL of anhydrous THF in a 3-neck flamed dried round bottom flask at −70° C. (acetone-dry ice bath) is slowly added the Grignard reagent prepared from bromopropionaldehyde dimethyl acetal (16.5 g, 90.4 mmol) and Mg turnings (4.39 g, 181 mmol) in anhydrous THF (250 mL), maintaining internal temperature around −68° C. to −70° C. After stirring at −70° C. for 2 hours, the reaction mixture is diluted with 200 mL of water with the dry ice bath removed. The mixture is poured into a separatory funnel, and the mixture is extracted 3 times with ethyl acetate (150 mL). The organic layers are combined and dried over Na2SO4 and the solvent evaporated leaving a thick yellow oil (11 g, 100% crude yield, MS ES+258.02).

Source