Sulfuric Acid → Methyl (E)-3-fluorocinnamate

HRID 2069182Notes

Reaction equation

HRID 2069182 reaction equation
[F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([OH:12])=[O:11])[CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[C:18]([O-])([O-])=O.[Na+].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]([O:12][CH3:18])=[O:11])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 1551219(2E)-3-(3-Fluorophenyl)-2-propenoic acid

Product 1

HCID 13415099Methyl (E)-3-fluorocinnamateYield 339.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (E)-3-(3-fluorophenyl)acrylic acid (5, 6.0 g, 32.7 mmol) in MeOH (150 mL) at 0° C. was added concentrated H2SO4 (3.0 mL) slowly. The reaction was heated under reflux for 24 h then cooled to room temperature and neutralized with Na2CO3 (1.0 g). The solvent was removed by rotary evaporation and the resulting yellow oil partitioned between EtOAc (300 mL) and saturated NaHCO3 (300 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (200 mL) and dried over Na2SO4. The solvent was removed by rotary evaporation to yield 6 as a low melting (<25° C.) white solid (32.0 mmol, 99%): 1H NMR (500 MHz, CDCl3) δ 3.79 (s, 3H), 6.39-6.43 (d, J=16.0 Hz, 1H), 7.04-7.07 (dt, J=2.0, 8.0 Hz, 1H), 7.18-7.20 (d, J=9.0 Hz, 1H), 7.25-7.26 (d, J=8.0 Hz, 1H), 7.30-7.35 (m, 1H), 7.60-7.64 (d, J=16.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 52.0, 114.4, 114.6, 117.3, 117.4, 119.4, 124.29, 124.32, 130.6, 130.7, 136.8, 136.9, 143.6, 143.7, 162.2, 164.2, 167.2; LCQ-MS (M+H+) calcd for C10H10FO2 181. found 181.

Workup

  1. temperatureThe reaction was heated
  2. temperatureunder reflux for 24 h
  3. customThe solvent was removed by rotary evaporation
  4. customthe resulting yellow oil partitioned between EtOAc (300 mL) and saturated NaHCO3 (300 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
  6. washThe combined organic layers were washed with brine (200 mL)
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-7208fa42ee1e4ddf8a0cab6066498b6b
Source dataset
uspto-grants-2012_10
Patent number
US08299100B2

Reaction notes

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