反应详情

To a solution of methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate (0.090 g, 0.21 mmol) in THF (1.0 mL) and water (1.0 mL) was added lithium hydroxide (0.025 g, 1.1 mmol). The solution was stirred at rt for 1 h, or until starting material was no longer observed by LCMS. The solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0) was added (pH was ca. 9-10). The mixture was acidified with 1N HCl to pH 6.0 and sonicated for 5 min. The aqueous solution was extracted with EtOAc (3×15 mL), and the separated organic extracts were dried over MgSO4, filtered and concentrated to afford a brown oil. The oil was dissolved in AcOH (3.0 mL), and the excess AcOH was removed under reduced pressure. Ether (15 mL) was added, and the resulting precipitate was collected by filtration. The brown solids were washed with water (10 mL) and chloroform (15 mL) to afford title compound as a yellow solid [hS1P1 EC50=1336 nM]. MS (ESI) m/z: Calculated: 414.1; Observed: 415.1 (M++1).

1. customThe solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0)
2. additionwas added (pH was ca. 9-10)
3. customsonicated for 5 min
4. extractionThe aqueous solution was extracted with EtOAc (3×15 mL)
5. dry with materialthe separated organic extracts were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto afford a brown oil
9. customthe excess AcOH was removed under reduced pressure
10. additionEther (15 mL) was added
11. filtrationthe resulting precipitate was collected by filtration
12. washThe brown solids were washed with water (10 mL) and chloroform (15 mL)