Carbon Dioxide → 3-Hydroxy-7-methoxy-3-methyl-phthalide

HRID 22174

Reaction equation

[CH3:1][O:2][C:3]1[CH:13]=[CH:12][CH:11]=[C:5]2[C:6]([O:8][C:9](=[O:10])[C:4]=12)=[O:7].[C:14](O)(=O)CC(O)=O.C(N(CC)CC)C.C(=O)=O>O>[OH:7][C:6]1([CH3:14])[C:5]2[C:4](=[C:3]([O:2][CH3:1])[CH:13]=[CH:12][CH:11]=2)[C:9](=[O:10])[O:8]1

Participants

Conditions

Temperature: 73 °C

Procedure

5.4 g of 3-methoxy-phthalic acid anhydride [see A. V. R. Rao et al., Indian J. Chem. 20B, 248 ff. (1981)], 4.7 g of malonic acid and 9 ml of triethylamine are heated slowly. The suspension becomes stirrable at 55° C. and, from 68° C., moderately vigorous CO2 evolution occurs. The internal temperature is maintained at 73° C. until gas evolution ceases (about 1 hour) and the reaction mixture is then heated at reflux temperature (internal temperature 85° C.) for a further 4 hours. When it has cooled, the reaction mixture is treated with water and extracted with ethyl acetate. The aqueous phase is then adjusted to pH 1.7 and extracted three times with fresh ethyl acetate, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. Fractional crystallisation (ethyl acetate/n-hexane) yields 3-hydroxy-7-methoxy-3-methyl-phthalide, m.p. 156°-158° C.; IR spectrum (CHCl3): C=O 1772 cm-1.

Workup

custombecomes stirrable at 55° C. and, from 68° C.
temperaturethe reaction mixture is then heated
temperatureat reflux temperature (internal temperature 85° C.) for a further 4 hours
temperatureWhen it has cooled
extractionextracted with ethyl acetate
extractionextracted three times with fresh ethyl acetate
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated by evaporation under reduced pressure
customFractional crystallisation (ethyl acetate/n-hexane)

Sources & evidence

ORD record: ord-321bce556ec0470c8cdb100a6ae37967
Source dataset: uspto-grants-1995_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05428002

Linked notes

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