反应详情

A solution of the diester from preparation 1 (44.3 g, 177 mmol) and 2,2′-(1,3-phenylene)diacetic acid (59.2 g, 308 mmol) in ethanol (24 mL) and dioxan (290 mL) was treated dropwise with 12M hydrochloric acid (4.9 mL, 58.8 mmol). The reaction mixture was stirred and heated under reflux for 18 hours before being allowed to cool and concentrated to low volume. The reaction mixture was diluted with toluene (125 mL) and the resulting slurry filtered. The filtrate was concentrated under reduced pressure and the residue taken up in water and neutralised with sodium bicarbonate. The mixture was diluted with ethyl acetate (200 mL) and the organic layer was separated and washed with sodium bicarbonate solution (5×30 mL) and brine (50 mL). The combined aqueous extracts were acidified to pH 3 with 6M hydrochloric acid and extracted with ether (3×30 mL). The organics were combined, dried over magnesium sulphate and concentrated under reduced pressure. The residue was triturated with pentane giving the title compound as a colourless solid 10.8 g.

1. temperatureheated
2. temperatureunder reflux for 18 hours
3. temperatureto cool
4. concentrationconcentrated to low volume
5. additionThe reaction mixture was diluted with toluene (125 mL)
6. filtrationthe resulting slurry filtered
7. concentrationThe filtrate was concentrated under reduced pressure
8. additionThe mixture was diluted with ethyl acetate (200 mL)
9. customthe organic layer was separated
10. washwashed with sodium bicarbonate solution (5×30 mL) and brine (50 mL)
11. extractionextracted with ether (3×30 mL)
12. dry with materialdried over magnesium sulphate
13. concentrationconcentrated under reduced pressure
14. customThe residue was triturated with pentane giving the title compound as a colourless solid 10.8 g