反应详情

温度

80 °C

To a solution of 1-naphthylmethanol (19.8 mg, 0.13 mmol) in anhydrous tetrahydrofuran were added potassium tert butoxide (0.14 mL, 1 M solution in anhydrous tetrahydrofuran 0.14 mmol) followed by a solution of methyl 3-cyano-4-fluorobenzoate (22.4 mg, 0.13 mmol) in dimethylsulfoxide (0.1 mL). The reaction mixture was shaken at 80° C. for 16 hours, evaporated in vacuo, and water (1 mL) was added. The mixture was extracted with ethyl acetate (3×1 mL) and the combined organic extracts were dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in tetrahydrofuran (0.7 mL), an aqueous solution of lithium hydroxide (0.7 mL, 1 M, 0.70 mmol) added and the mixture was shaken at 60° C. for 2 hours. The reaction mixture was evaporated in vacuo and hydrochloric acid (0.70 mL, 1 M, 0.70 mmol) was added. The resulting mixture was extracted with ethyl acetate (3×1 mL) and the combined organic extracts were dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. To the residue were added methanesulfonamide (27 mg, 0.28 mmol), a solution of 4-dimethylaminopyridine (24.4 mg, 0.20 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38.3 mg, 0.20 mmol) in dichloromethane (1 mL). The mixture was shaken for 16 hours at 30° C. and then evaporated in vacuo. The residue was purified on an HPLC column (Grace Vydac C18 200*20 mm*5 mm column) with a gradient of acetonitrile/water (0.1% trifluoroacetic acid) to yield the title compound (4.25 mg, 9%).

1. customevaporated in vacuo, and water (1 mL)
2. additionwas added
3. extractionThe mixture was extracted with ethyl acetate (3×1 mL)
4. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
5. filtrationfiltered
6. customevaporated in vacuo
7. dissolutionThe residue was dissolved in tetrahydrofuran (0.7 mL)
8. stirringthe mixture was shaken at 60° C. for 2 hours
9. additionwas added
10. extractionThe resulting mixture was extracted with ethyl acetate (3×1 mL)
11. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
12. filtrationfiltered
13. customevaporated in vacuo
14. stirringThe mixture was shaken for 16 hours at 30° C.
15. customevaporated in vacuo
16. customThe residue was purified on an HPLC column (Grace Vydac C18 200*20 mm*5 mm column) with a gradient of acetonitrile/water (0.1% trifluoroacetic acid)