Hydrochloric Acid → (3-ForMyl-phenyl)-acetic acid

To a solution of 2-(m-tolyl)acetic acid in chloroform (30 mL) was added N-bromosuccinimide (2.37 g, 13.32 mmol). The mixture was heated to reflux for 8 hours and the solvent was removed in vacuo. The residue was dissolved in ethanol (30 mL) and water (30 mL) and hexamethylenetetramine (5 g, 35.7 mmol) was added. The mixture was heated to reflux for 4 hours. Concentrated HCl (5.9 mL) was added cautiously to the mixture at reflux. The mixture was heated to reflux for 30 minutes and then allowed to cool. Water (30 mL) and DCM (30 mL) were added and the organic phase was passed through a hydrophobic frit and the solvent was removed in vacuo. The residue was taken up into saturated aqueous sodium bicarbonate solution, and washed with DCM (2×15 mL). The aqueous phase was acidified with 2M aqueous HCl. The mixture was extracted with DCM (2×15 mL) and the combined organic fractions were passed through a hydrophobic frit. The solvent was removed in vacuo to afford a mixture of the title compound as an off-white solid (1.35 g, 62%). 1H NMR (400 MHz, CDCl3): δ 10.01 (s, 1H), 7.84-7.79 (m, 2H), 7.60-7.48 (m, 2H), 3.75 (s, 2H). LCMS (Method 1): [MH+]=165 at 2.77 min.

1. temperatureThe mixture was heated
2. temperatureto reflux for 8 hours
3. customthe solvent was removed in vacuo
4. dissolutionThe residue was dissolved in ethanol (30 mL)
5. temperatureThe mixture was heated
6. temperatureto reflux for 4 hours
7. temperatureat reflux
8. temperatureThe mixture was heated
9. temperatureto reflux for 30 minutes
10. temperatureto cool
11. customthe solvent was removed in vacuo
12. washwashed with DCM (2×15 mL)
13. extractionThe mixture was extracted with DCM (2×15 mL)
14. customThe solvent was removed in vacuo
15. customto afford

ORD record

ord-0c4b51d95aed440a85019d744b938597

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090606B2