Hydrochloric Acid → 4-Fluoro-2,3-dihydroxybenzaldehyde

Magnesium chloride (3.71 g, 33 mmol) was added portionwise at room temperature to a solution of 3-fluorocatechol (2 g, 15.6 mmol) in acetonitrile (20 mL), followed by triethylamine (13.4 mL, 97.5 mmol). Paraformaldehyde (3.16 g, 105.3 mmol) was then added to the stirred suspension and the mixture was heated at reflux for 5 hours. The mixture was cooled to room temperature then poured into a mixture of 5% HCl and TBME. The organic phase was separated, and the aqueous layer re-extracted with TBME. The combined organic extracts were washed with brine, dried over sodium sulphate and the solvent removed under reduced pressure. The crude mixture (˜1:1 starting material:product) was purified on normal silica in neat DCM followed by DCM/MeOH 96:4 and 90:10 to yield 478 mg of 28 still contaminated with 11.4% w/w of 3-fluorocatechol.

1. temperaturethe mixture was heated
2. temperatureat reflux for 5 hours
3. customThe organic phase was separated
4. extractionthe aqueous layer re-extracted with TBME
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over sodium sulphate
7. customthe solvent removed under reduced pressure
8. customThe crude mixture (˜1:1 starting material:product) was purified on normal silica in neat DCM

ORD record

ord-87e79cbc614f479d95cef12d52eb50aa

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198302B2