反应详情

A solution of 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 hydrochloric acid (12 M, 4.9 mL, 58.8 mmol). The reaction mixture was stirred at 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 in vacuo and the residue taken up in water and basified with sodium bicarbonate until pH neutral. 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 diethylether (3×30 mL). The organics were combined, dried (MgSO4) and concentrated in vacuo. The residue was triturated with pentane to yield a colourless solid (10.8 g). 1HNMR (CD3OD, 400 MHz) δ: 1.25 (3H, t), 3.60 (2H, m), 3.63 (2H, m), 4.15 (2H, q), 7.18–7.32 (4H, m); LRMS ESI m/z 245 [M+Na]+

1. temperatureat reflux for 18 hours
2. temperatureto cool
3. concentrationconcentrated to low volume
4. additionThe reaction mixture was diluted with toluene (125 mL)
5. filtrationthe resulting slurry filtered
6. concentrationThe filtrate was concentrated in vacuo
7. additionThe mixture was diluted with ethyl acetate (200 mL)
8. customthe organic layer was separated
9. washwashed with sodium bicarbonate solution (5×30 ml) and brine (50 mL)
10. extractionextracted with diethylether (3×30 mL)
11. dry with materialdried (MgSO4)
12. concentrationconcentrated in vacuo
13. customThe residue was triturated with pentane