Methanol, magnesium salt (2:1) → 2-Hydroxy-5-(2-methoxyethoxy)benzaldehyde

A solution of 4-(2-methoxyethoxy)phenol in toluene (350 ml) was added to a solution of magnesium methoxide in methanol (8% by weight solution, 331 mls), under an atmosphere of argon. The reaction mixture was heated at reflux for 2 hours. Toluene (350 mls) was added and the reaction mixture distilled at atmospheric pressure until the internal temperature reached 92° C. A mixture of paraformaldehyde in toluene (300 ml) was added to the reaction mixture and the reaction mixture was heated at reflux for 3.5 hours. The mixture was cooled to ambient temperature and then stirred at ambient temperature for 18 hours. The reaction mixture was diluted with toluene (400 ml), washed with 2M aqueous hydrochloric acid (2×150 ml) and water (to pH 1). The residue was distilled under vacuum to give 2-hydroxy-5-(2-methoxyethoxy)benzaldehyde as an oil (35 g), bp 104-130° C. [0.01 mm Hg]; NMR(CDCl3): 3.45(3H,s), 3.75(2H,m), 4.12(2H,m), 6.92(1H,d), 7.05(1H,d), 7.2(1H,dd), 9.84(1H,s) and 10.63(1H,s); m/z 197(M+H).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 2 hours
3. distillationthe reaction mixture distilled at atmospheric pressure until the internal temperature
4. customreached 92° C
5. additionA mixture of paraformaldehyde in toluene (300 ml)
6. additionwas added to the reaction mixture
7. temperaturethe reaction mixture was heated
8. temperatureat reflux for 3.5 hours
9. additionThe reaction mixture was diluted with toluene (400 ml)
10. washwashed with 2M aqueous hydrochloric acid (2×150 ml) and water (to pH 1)
11. distillationThe residue was distilled under vacuum

ORD record

ord-c764ca2453b2498ab05b347fb7143d8b

Source dataset

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05919793