4-Fluorostyrene → Methyl 2-[2-(4-fluorophenyl)ethenyl]-5-methoxybenzoate

HRID 1251890Notes

Reaction equation

HRID 1251890 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH2:20])=[CH:17][CH:16]=1.C([O-])(O)=O.[Na+]>O>[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[CH:20][C:2]2[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 678834-FluorostyreneHCID 516892Sodium BicarbonateHCID 2776849Methyl 2-bromo-5-methoxybenzoate

Product 1

HCID 53733998Methyl 2-[2-(4-fluorophenyl)ethenyl]-5-methoxybenzoateYield 132.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of methyl 2-bromo-5-methoxybenzoate (28.3 g, 115 mmol), 4-fluorostyrene (20.6 ml, 173.3 mmol), tert-n-butylamine (2.7 ml, 11.5 mmol), Pd[(o-tolyl)3 P]2 Cl2 (0.9 g, 1.15 mmol), and NaHCO3 (14.6 g, 173.3 mmol), and water (220 ml) was stirred and heated at reflux for 16 hours. The reaction mixture was diluted with water (200 ml) and extracted with ethyl acetate (2×400 ml). The extracts were washed with 2M HCl (100 ml), water (100 ml), brine (100 ml), dried (MgSO4), filtered and evaporated to dryness. The brown gum obtained was purified by chromatography on silica (90 g, Biotage column), eluting with a gradient of ethyl acetate in iso-hexane (0%-20% ethyl acetate). The relevant fractions were combined and evaporated to give methyl 2-[2-(4-fluorophenyl)ethenyl]-5-methoxybenzoate, (43.5 g)

Workup

  1. temperatureheated
  2. temperatureat reflux for 16 hours
  3. extractionextracted with ethyl acetate (2×400 ml)
  4. washThe extracts were washed with 2M HCl (100 ml), water (100 ml), brine (100 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe brown gum obtained
  9. customwas purified by chromatography on silica (90 g, Biotage column)
  10. washeluting with a gradient of ethyl acetate in iso-hexane (0%-20% ethyl acetate)
  11. customevaporated

Sources & evidence

ORD record
ord-411cd54c8b9148d0a29949ccbaa019ae
Source dataset
uspto-grants-2002_01
Patent number
US06342765B1

Reaction notes

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