Sodium Carbonate → Methyl 2-fluoro-6-vinylbenzoate

HRID 1476808Notes

Reaction equation

HRID 1476808 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[B-](F)(F)(F)[CH:14]=[CH2:15].[K+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:2]([CH:14]=[CH2:15])[C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 12192163Methyl 2-bromo-6-fluorobenzoateHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 90387241Methyl 2-fluoro-6-vinylbenzoateYield 76.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-bromo-6-fluorobenzoate (53 g, 0.228 mol) and potassium trifluoro(vinyl)borate (33.63 g, 0.251 mol) in dioxane and H2O (3:1, 600 mL) was added Pd(dppf)Cl2 (5 g, 6.84 mmol) and sodium carbonate (69 g, 0.684 mol) at RT. The reaction mixture was heated at 100° C. for 12 hours under a nitrogen atmosphere. The mixture was concentrated in vacuo, diluted with water, and extracted with EtOAc (3×200 mL). The combined organic layers were washed with brine, dried over anhydrous Na2CO3, filtered, and concentrated. The crude product was purified by column chromatography eluting with a gradient of EtOAc (1-100%) and PE to give the title compound (31.4 g, 76.5%). 1H NMR (400 MHz, CDCl3) δ ppm 7.45-7.36 (m, 2H), 7.03-7.02 (m, 1H), 6.88-6.81 (m, 1H), 5.77-5.73 (m, 1H), 5.41-5.39 (d, J=10.8 Hz, 1H), 3.95 (s, 3H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with EtOAc (3×200 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous Na2CO3
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography
  9. washeluting with a gradient of EtOAc (1-100%) and PE

Sources & evidence

ORD record
ord-a4392b2c6ba3477d98f7fc0f1cb93bf9
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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