Acetic Acid → 6-Methoxyphthalide

A mixture of 20 g (131 mmol) of 3-methoxybenzoic acid, 13 ml (160 mmol) of 37% strength formalin soln., 16 ml (162 mmol) of 37% strength HCl and 150 ml of 100% strength acetic acid is heated to 90° C., while stirring. After a clear solution has formed, the stirrer is switched off and the mixture is left at this temperature for 14 hours. The acetic acid is stripped off at 80° C. in vacuo, the residue is taken up in 150 ml of toluene and the mixture is concentrated to 80 ml. The 80° C. hot solution is washed with 40 ml portions of 20% strength Na2SO4 solution until the pH of the aqueous solution is alkaline, and is then washed with 40 ml of H2O. After addition of 6 ml of morpholine, the organic phase is stirred at 80° C. for 2 h and then washed with 50 ml portions of 10% strength H2SO4 until the aqueous phase is acidic, and twice with 50 ml of H2O each time. For crystallization of the product, the mixture is concentrated to 50 ml, a seed crystal is added if necessary, and the mixture is stirred until it has cooled to room temperature. The product is obtained by filtering off in the form of white crystals.

1. customAfter a clear solution has formed
2. customis stripped off at 80° C. in vacuo
3. concentrationthe mixture is concentrated to 80 ml
4. washThe 80° C. hot solution is washed with 40 ml portions of 20% strength Na2SO4 solution until the pH of the aqueous solution
5. washis then washed with 40 ml of H2O
6. additionAfter addition of 6 ml of morpholine
7. stirringthe organic phase is stirred at 80° C. for 2 h
8. washwashed with 50 ml portions of 10% strength H2SO4 until the aqueous phase
9. customFor crystallization of the product
10. concentrationthe mixture is concentrated to 50 ml
11. additiona seed crystal is added if necessary, and the mixture
12. stirringis stirred until it
13. customThe product is obtained
14. filtrationby filtering off in the form of white crystals

ORD record

ord-c2cd3d5beb7a4a228ac495a21931e7c7

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633312B2