反应详情

Methyl 3-bromo-4-iso-propyloxybenzoate (828 mg; 3.03 mmol) was dissolved in DMF (25 ml) and treated with potassium trifluoroacetate (922 mg; 6.06 mmol), copper (I) iodide (1.15 g; 6.06 mmol) and toluene (50 ml). The resulting mixture was heated at reflux for 1.5 h under Dean and Stark conditions with removal of ca 50 ml of distillate. The resulting mixture was heated at reflux for 18 h then cooled to room temperature, before being poured into a mixture of Et2O (100 ml) and HO (100 ml). The two-phase mixture was stirred at room temperature for 0.5 h then filtered through Celite. The two phases in the filtrate were separated, the aq. phase further extracted with Et2O (50 ml) and the organic extracts combined, washed with saturated, aq. Na2S2O3, H2O, saturated brine, dried (MgSO4) and evaporated to dryness under reduced pressure to give a brown oil. This brown oil was dissolved in MeOH (ca 20 ml) and treated with 2M aq. sodium hydroxide solution (2 ml; 4 mmol) and the resulting solution heated at reflux for 3h. The volatiles were removed under reduced pressure and the residue partitioned between EtOAc and H2O. The phases were separated, the aq. phase acidified to pH1 with 2M hydrochloric acid in the presence of EtOAc and the phases separated. The aq. phase was further extracted with EtOAc, the extracts combined, washed with H2O, saturated brine, dried (MgSO4) and evaporated to dryness underreduced pressure to give the title compound as a white solid. (671 mg; 89%).

1. temperatureThe resulting mixture was heated
2. temperatureat reflux for 1.5 h under Dean and Stark conditions with removal of ca 50 ml of distillate
3. temperatureThe resulting mixture was heated
4. temperatureat reflux for 18 h
5. filtrationthen filtered through Celite
6. customThe two phases in the filtrate were separated
7. extractionthe aq. phase further extracted with Et2O (50 ml)
8. washwashed with saturated, aq. Na2S2O3, H2O, saturated brine
9. dry with materialdried (MgSO4)
10. customevaporated to dryness under reduced pressure
11. customto give a brown oil
12. temperaturethe resulting solution heated
13. temperatureat reflux for 3h
14. customThe volatiles were removed under reduced pressure
15. customthe residue partitioned between EtOAc and H2O
16. customThe phases were separated
17. customthe phases separated
18. extractionThe aq. phase was further extracted with EtOAc
19. washwashed with H2O, saturated brine
20. dry with materialdried (MgSO4)
21. customevaporated to dryness underreduced pressure