反应详情

温度

80 °C

To a solution of ethyl 3-{[5-(biphenyl-4-yl)-6-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-2-yl]oxy}cyclopentanecarboxylate (80 mg, 0.135 mmol) in 2.7 mL of THF was added TBAF (0.700 mL, 0.700 mmol) dropwise via syringe. The reaction was heated at 80° C. for 1.5 h. After heating for 4 h, the reaction was concentrated and the residue was re-dissolved in 4 mL of MeOH and treated with 1 mL of 2.5 N NaOH. The reaction was maintained at ambient temperature overnight. Then the solvent was removed and the resulting residue was dissolved in H2O and acidified to pH 1 with 2 N HCl. The aqueous layer was separated and extracted with EtOAc. The combined organic layers were washed with 2 N HCl, H2O, and brine. The combined organic layers were then dried over Na2SO4, filtered, and concentrated. Purification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O) afforded a 1:1 cis/trans mixture of the title compound as a white solid. LCMS: calculated for C25H21ClN2O3 432.89, observed m/e 432.93 M+ (Rt 2.13/4 min). 1H NMR (500 MHz, CD3OD): δ7.7.72-7.63 (m, 8H), 7.58-7.55 (m, 2H), 7.49 (d, 4H), 7.47-7.42 (m, 4H), 7.42-7.38 (m, 2H), 7.37-7.32 (m, 2H), 5.54-5.47 (m, 1H), 5.46-5.40 (m, 1H), 3.16-3.05 (m, 1H), 3.05-2.95 (m, 1H), 2.54-2.43 (m, 1H), 2.42-2.31 (m, 3H), 2.31-1.95 (m, 8H).

1. temperatureAfter heating for 4 h
2. concentrationthe reaction was concentrated
3. dissolutionthe residue was re-dissolved in 4 mL of MeOH
4. additiontreated with 1 mL of 2.5 N NaOH
5. temperatureThe reaction was maintained at ambient temperature overnight
6. customThen the solvent was removed
7. dissolutionthe resulting residue was dissolved in H2O
8. customThe aqueous layer was separated
9. extractionextracted with EtOAc
10. washThe combined organic layers were washed with 2 N HCl, H2O, and brine
11. dry with materialThe combined organic layers were then dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customPurification of the resulting residue by reverse phase Gilson™ HPLC (30-100% MeCN/H2O)
15. customafforded