Reaction #1596943

Reaction equation

hydrochloric acid

1-benzyloxy-4-bromo-2-fluorobenzene

N-formylmorpholine

magnesium

→

4-benzyloxy-3-fluorobenzaldehyde

Solvents

MTBE

THF

THF

THF

THF

Conditions

Workup

1. 1
   Temperaturea gentle reflux
2. 2
   Temperatureis maintained
3. 3
   Otherafter initiation of the Grignard reaction
4. 4
   workup.ADDITIONWhen the addition
5. 5
   Temperaturethe batch is heated at the boil for 1 h
6. 6
   OtherThe organic phase is separated off
7. 7
   Extractionthe aqueous phase is extracted with MTBE
8. 8
   WashThe combined organic phases are washed with saturated sodium chloride solution
9. 9
   Otherdried
10. 10
    ConcentrationThe solution is concentrated to dryness
11. 11
    Otherthe crude product is recrystallised from n-heptane

Procedure

25.9 g (1.07 mol) of magnesium turnings are initially introduced in 200 ml of THF, and a solution of 285.6 g (1.02 mol) of 1-benzyloxy-4-bromo-2-fluorobenzene in 700 ml of THF is added dropwise at such a rate that a gentle reflux is maintained after initiation of the Grignard reaction. When the addition is complete, the mixture is diluted with 1000 ml of THF, and the batch is heated at the boil for 1 h. The solution of the Grignard reagent is cooled to 0° C., and 118 ml (1.07 mol) of N-formylmorpholine in 100 ml of THF are added dropwise. After 1 h, the mixture is diluted with MTBE and hydrolysed using dilute hydrochloric acid. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with saturated sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the crude product is recrystallised from n-heptane:MTBE.

Source