6-Bromo-2-fluoro-3-methoxybenzaldehyde → 2-Fluoro-3-methoxy-6-vinylbenzaldehyde

HRID 222314Notes

Reaction equation

HRID 222314 reaction equation
Br[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([F:10])[C:5]([O:11][CH3:12])=[CH:4][CH:3]=1.[CH:13]([B-](F)(F)F)=[CH2:14].[K+]>C(O)CC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:10][C:6]1[C:5]([O:11][CH3:12])=[CH:4][CH:3]=[C:2]([CH:13]=[CH2:14])[C:7]=1[CH:8]=[O:9]

Participants

5

Reactant 2

HCID 231579156-Bromo-2-fluoro-3-methoxybenzaldehydeHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 577227732-Fluoro-3-methoxy-6-vinylbenzaldehyde

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 10311-PropanolSolvent

Procedure

To a stirred solution of 6-bromo-2-fluoro-3-methoxybenzaldehyde (13 g, 56 mmol) in nPrOH (200 mL) were added potassium vinyltrifluoroborate (7.9 g, 59 mmol), PdCl2(dppf) (0.91 g, 1.1 mmol), and TEA (7.8 mL, 56 mmol). The reaction mixture was purged with N2 for 10 min, heated to reflux for 3 h, cooled to room temperature, treated with water, and concentrated. The residue was extracted with EtOAc (×3). The combined organics were washed with brine, dried (Na2SO4), concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 10.53 (s, 1H); 7.43 (dd, 1H); 7.31 (d, 1H); 7.16 (t, 1H); 5.60 (d, 1H); 5.36 (d, 1H); 3.95 (s, 3H).

Workup

  1. customThe reaction mixture was purged with N2 for 10 min
  2. temperatureheated
  3. temperatureto reflux for 3 h
  4. additiontreated with water
  5. concentrationconcentrated
  6. extractionThe residue was extracted with EtOAc (×3)
  7. washThe combined organics were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-bd8e3e39fc5340a6bf66c7f53c006236
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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