Dimethylformamide → 2-(Benzyloxy)-4-fluorobenzaldehyde

HRID 324871Notes

Reaction equation

HRID 324871 reaction equation
[Mg].[CH2:2]([O:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN([CH:20]=[O:21])C>C1COCC1.C(OC1C=C(F)C=CC=1)C1C=CC=CC=1>[CH2:2]([O:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[CH:20]=[O:21])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 5462224MagnesiumHCID 116298011-(Benzyloxy)-3-fluorobenzene

Product 1

HCID 106809572-(Benzyloxy)-4-fluorobenzaldehyde

Reagents, catalysts & solvents 2

HCID 116298011-(Benzyloxy)-3-fluorobenzeneCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a slurry of magnesium (9.52 g, 0.39 mol) in THF (25 mL) in a 1 L round bottom flask fitted with a condenser was added the intermediate obtained in Step A (1 g). A vigorous reflux commenced at once. To this refluxing mixture was added a solution of the intermediate from Step A (109 g) at a rate which maintained reflux. After completion of addition the reaction was allowed to proceed until it cooled to 25° C. and was then heated at reflux for 1 h. The reaction was allowed to cool to 25° C. and DMF (48 mL) was then added portionwise. The reaction was allowed to cool to 25° C. and was then filtered through a plug of Celite. The THF was removed under reduced pressure and the residue was dissolved in ethyl acetate (500 mL) and washed sequentially with water (100 mL), 10% HCl (100 mL), saturated sodium bicarbonate solution (100 mL), and brine (100 mL). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The resultant residue was purified by flash chromatography (10% ethyl acetate-hexane) to provide 77.3 g of 2-benzyloxy-4-fluorobenzaldehyde. 1H NMR (300 MHz, CDCl3): δ 5.16 (s, 2 H), 6.70-6.76 (m, 2 H), 7.34-7.44 (m, 5 H), 7.87-7.92 (m, 1 H), 10.43 (s, 1 H). FAB-MS: calcd for (C14H11O2F) 230; found 231 (M+1).

Workup

  1. temperatureA vigorous reflux
  2. temperaturemaintained
  3. temperaturereflux
  4. additionAfter completion of addition the reaction
  5. temperaturewas then heated
  6. temperatureat reflux for 1 h
  7. temperatureto cool to 25° C.
  8. temperatureto cool to 25° C.
  9. filtrationwas then filtered through a plug of Celite
  10. customThe THF was removed under reduced pressure
  11. dissolutionthe residue was dissolved in ethyl acetate (500 mL)
  12. washwashed sequentially with water (100 mL), 10% HCl (100 mL), saturated sodium bicarbonate solution (100 mL), and brine (100 mL)
  13. dry with materialThe organic layer was dried (Na2SO4)
  14. concentrationconcentrated under reduced pressure
  15. customThe resultant residue was purified by flash chromatography (10% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-533d9ca584244e65905c95d514b02d55
Source dataset
uspto-grants-2001_04
Patent number
US06218431B1

Reaction notes

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