Hydrochloric Acid → 3-(2-Fluorophenyl)prop-2-ynoic acid

HRID 1837942Notes

Reaction equation

HRID 1837942 reaction equation
Cl.OO.[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[C:12][CH:13]=[O:14].[O-:15]Cl=O.[Na+]>O.CC#N.[O-]Cl=O.[Na+]>[F:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[C:12][C:13]([OH:15])=[O:14]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 226776583-(2-Fluorophenyl)prop-2-ynalHCID 23668197Sodium Chlorite

Product 1

HCID 226776553-(2-Fluorophenyl)prop-2-ynoic acidYield 86%

Reagents, catalysts & solvents 3

HCID 23668197Sodium ChloriteCatalystHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent

Procedure

A mixture of NaH2PO4 (37 g, 0.3 mol, 0.3 equiv) in water (330 mL) buffered to pH 2 with conc. HCl and H2O2 (30%, 112 mL, 1.1 mol, 1.1 equiv) was added to a solution of 3-(2-fluorophenyl)prop-2-ynal (151 g, 1.02 mol) in CH3CN (830 mL). The resulting mixture was cooled in an ice bath and was treated slowly with a solution of NaClO2 (102 g, 1.1 mol, 1.1 equiv) in water (1.1 L), keeping the temperature below 10° C. After 30 min a solution of NaClO2 (5.8 g, 64 mmol, 0.06 equiv) in water (50 mL) was added. After another 30 min the layers were separated and the aqueous layer was washed with EtOAc (3×500 mL). The organic layers were combined and back-extracted with a saturated NaHCO3 solution (3×500 mL). The aqueous layers were combined, acidified to pH 1 with conc. HCl and extracted with EtOAc (3×500 mL). The combined organic layers were washed with a saturated NaCl solution (1 L), dried (Na2SO4) and concentrated under reduced pressure to give 3-(2-fluorophenyl)prop-2-ynoic acid (144 g, 86%) as a yellow solid: TLC (1% AcOH/CH2Cl2) Rf 0.34; 1H NMR (CDCl3+d4-MeOH) δ 6.98-7.08 (m, 2H), 7.29-7.48 (m, 2H), 12.77 (br s, 1H); 13C NMR (CDCl3+d4-MeOH) δ 78.3, 85.7 (d, JC−F=2.5 Hz, 1C), 108.3 (d, JC−F=15.8 Hz, 1C), 115.4 (d, JC−F=20.7 Hz, 1C), 124.0, 132.1 (d, JC−F=7.3 Hz, 1C), 134.1 (d, JC−F=9.8 Hz, 1C), 135.2, 154.8, 163.1 (d, JC−F=256.1 Hz, 1C).

Workup

  1. temperatureThe resulting mixture was cooled in an ice bath
  2. customthe temperature below 10° C
  3. customAfter another 30 min the layers were separated
  4. washthe aqueous layer was washed with EtOAc (3×500 mL)
  5. extractionback-extracted with a saturated NaHCO3 solution (3×500 mL)
  6. extractionextracted with EtOAc (3×500 mL)
  7. washThe combined organic layers were washed with a saturated NaCl solution (1 L)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2727a827867440019f32377ae0bb7887
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

Loading…