4-Hydroxybenzoic Acid → 4-(2-Methoxyethoxy)benzoic acid

Commercially available 4-hydroxy benzoic acid (10.0 g, 72.4 mmol) and 2-chloroethylmethylether (13.7 g, 144 mmol) wer added to a stirred, room temperature solution of KOH (8.12 g, 144 mmol) in ethanol (90 mL) water (10 mL) and the resulting yellow solution was heated at reflux for 20 hours. The reaction mixture was cooled to room temperature and concentrated to provide a light yellow powder. The reaction mixtur was diluted with water (100 mL) and addtional KOH (5 g, 89 mmol) was added and the reaction mixture was heated at reflux for two hours. The reaction mixture was cooled to 0° C., and neutralized with 2M HCl (100 mL). The precipitate was filtered and the off white powder (15.5 g) was chromatographed (silica gel, elutent 95:5/methylene chloride: methanol) to provide the title compound as a white powder (8.73 g, 54%): 1HNMR (CDCl3) δ3.37 (s, 3H), 3.69 (t, J=5 Hz, 2H), 4.16 (t, J=5 Hz, 2H), 6.97 (d, J=9 Hz, 2H), 7.86 (d, J=9 Hz, 2H), 12.52 (s, 1); MS (ESI): [M−H]− at m/z 196.

1. temperaturethe resulting yellow solution was heated
2. temperatureat reflux for 20 hours
3. concentrationconcentrated
4. customto provide a light yellow powder
5. additionwas added
6. temperaturethe reaction mixture was heated
7. temperatureat reflux for two hours
8. temperatureThe reaction mixture was cooled to 0° C.
9. filtrationThe precipitate was filtered
10. customthe off white powder (15.5 g) was chromatographed (silica gel, elutent 95:5/methylene chloride: methanol)

ORD record

ord-66ca28ed26634bea8edf9dd8934c6826

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06355633B1