Hydrochloric Acid → 4-(Benzyloxy)-3-fluorobenzaldehyde

HRID 1509761Notes

Reaction equation

HRID 1509761 reaction equation
[Mg].[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][C:11]=1[F:17])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:18](N1CCOCC1)=[O:19].Cl>C1COCC1.CC(OC)(C)C>[CH2:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:18]=[O:19])=[CH:12][C:11]=1[F:17])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 20417N-FormylmorpholineHCID 5462224MagnesiumHCID 187574911-(Benzyloxy)-4-bromo-2-fluorobenzene

Product 1

HCID 219768984-(Benzyloxy)-3-fluorobenzaldehyde

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 15413tert-Butyl methyl etherSolvent

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.

Workup

  1. temperaturea gentle reflux
  2. temperatureis maintained
  3. customafter initiation of the Grignard reaction
  4. additionWhen the addition
  5. temperaturethe batch is heated at the boil for 1 h
  6. customThe organic phase is separated off
  7. extractionthe aqueous phase is extracted with MTBE
  8. washThe combined organic phases are washed with saturated sodium chloride solution
  9. customdried
  10. concentrationThe solution is concentrated to dryness
  11. customthe crude product is recrystallised from n-heptane

Sources & evidence

ORD record
ord-1677698e90ce4f79b5758bcb5300d808
Source dataset
uspto-grants-2012_07
Patent number
US08211513B2

Reaction notes

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