반응 #595588

반응 방정식

1-naphthylmethanol

potassium tert butoxide

hydrochloric acid

methyl 3-cyano-4-fluorobenzoate

lithium hydroxide

methanesulfonamide

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

title compound

수율 9.0%

3-Cyano-N-(methylsulfonyl)-4-(1-naphthylmethoxy)benzamide

수율 9.0%

용매

dichloromethane

tetrahydrofuran

dimethylsulfoxide

반응 조건

후처리

1. 1
   기타evaporated in vacuo, and water (1 mL)
2. 2
   workup.ADDITIONwas added
3. 3
   추출The mixture was extracted with ethyl acetate (3×1 mL)
4. 4
   건조the combined organic extracts were dried over anhydrous sodium sulphate
5. 5
   여과filtered
6. 6
   기타evaporated in vacuo
7. 7
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (0.7 mL)
8. 8
   workup.STIRRINGthe mixture was shaken at 60° C. for 2 hours
9. 9
   workup.ADDITIONwas added
10. 10
    추출The resulting mixture was extracted with ethyl acetate (3×1 mL)
11. 11
    건조the combined organic extracts were dried over anhydrous sodium sulphate
12. 12
    여과filtered
13. 13
    기타evaporated in vacuo
14. 14
    workup.STIRRINGThe mixture was shaken for 16 hours at 30° C.
15. 15
    기타evaporated in vacuo
16. 16
    기타The 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)

실험 절차

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%).

출처