Hydrochloric Acid → 6-Methoxyphthalide

Temperatur

100 °C

Formaldehyde 48% v/v (65 ml, 0.86 moles) under stirring, then 3-methoxy-benzoic acid (100 g, 0.66 moles) were added to concentrated HCl (1 l) and the mixture was heated at 100° C. by checking the development of gas for 30 minutes. The cooling of the mixture brought to the formation of a precipitate which was filtered and put aside, while the mixture was washed with water, then with 5% NaOH. The new precipitate was extracted twice with CH2Cl2, the extract was anhydrified, concentrated, joined to the previously filtered solid, and both were dissolved in CH2Cl2 and treated with diethylamine (120 ml, 1.15 moles). After 24 hours it was extracted with 10% HCl and the phases were separated with CH2Cl2. The organic phase was washed with 10% NaOH, decoloured with charcoal, anhydrified and concentrated. The residue was dissolved in CH2Cl2 and treated, under stirring, with 10% HCl for 30 minutes. The organic phase was washed with water, anhydrified and concentrated. The residue was dissolved in CH2Cl2 and treated with 10% NaOH under stirring for 30 minutes. The organic phase was washed with water, dried and concentrated to give a solid which was crystallised from aqueous CH3OH. The filtrate was dried at 50° C. on P2O5, then crystallised again from aqueous CH3OH to give 35.28 g of the title compound (yield: 32%).

1. customfor 30 minutes
2. temperatureThe cooling of the mixture
3. filtrationwas filtered
4. washwas washed with water
5. extractionThe new precipitate was extracted twice with CH2Cl2
6. concentrationconcentrated
7. dissolutionboth were dissolved in CH2Cl2
8. extractionAfter 24 hours it was extracted with 10% HCl
9. customthe phases were separated with CH2Cl2
10. washThe organic phase was washed with 10% NaOH
11. concentrationconcentrated
12. dissolutionThe residue was dissolved in CH2Cl2
13. additiontreated
14. washThe organic phase was washed with water, anhydrified
15. concentrationconcentrated
16. dissolutionThe residue was dissolved in CH2Cl2
17. additiontreated with 10% NaOH
18. stirringunder stirring for 30 minutes
19. washThe organic phase was washed with water
20. customdried
21. concentrationconcentrated
22. customto give a solid which
23. customwas crystallised from aqueous CH3OH
24. customThe filtrate was dried at 50° C. on P2O5
25. customcrystallised again from aqueous CH3OH

ORD-Eintrag

ord-80c1a526b63746049fa46f3e1e3b6b12

Quelldatensatz

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06525055B1