反应详情

温度

-20 °C

n-Butyllithium (23.04 mL, 57.6 mmol) was dissolved in tetrahydrofuran (THF) (100 mL) at −20° C. 2,2,6,6-tetramethylpiperidine (9.72 mL, 57.6 mmol) was added dropwise and stirred for 15 minutes maintaining a temperature of −20° C. The solution was cooled to −78° C. whereupon 2,3-dichlorobenzoic acid (5 g, 26.2 mmol, commercially available from e.g. Sigma-Aldrich, Alfa Aesar or Fluorochem) dissolved in Tetrahydrofuran (THF) (50 mL) was added dropwise. The solution was stirred at −78° C. for 1 hour whereupon iodomethane (6.55 mL, 105 mmol) was added dropwise and the mixture allowed to reach room temperature overnight. Solvents were removed in vacuo and the residue partitioned between ethyl acetate (100 mL) and 5N HCl (50 mL). The aqueous phase was extracted with ethyl acetate (3×50 mL), combined extracts were washed with water (50 mL), brine (50 mL) dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a crude solid in 5.90 g.

1. additionwas added dropwise
2. additionwas added dropwise
3. waitto reach room temperature overnight
4. customSolvents were removed in vacuo
5. customthe residue partitioned between ethyl acetate (100 mL) and 5N HCl (50 mL)
6. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
7. washwere washed with water (50 mL), brine (50 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated in vacuo
10. customto afford a crude solid in 5.90 g