反应详情

Add dropwise a solution of 3,3-dimethyl-1,5-dioxa-spiro[5.5]undecan-9-ol, (NE4-A05445-029, 1377 mg, 6.88 mmol) in DMF (2.0 mL) to a suspension of sodium hydride (412 mg, 10.32 mmol) in DMF (8.0 mL). Let the reaction mixture stir at room temperature for 1 h, then heat while stirring at 50° C. for 20 minutes (min). Add dropwise a solution of 4-fluoro-benzonitrile (1000 mg, 8.26 mmol) in DMF (4.2 mL). Continue the heating at 60° C. and stirring for 2 hours (h). Concentrate the reaction mixture to remove DMF. Wash the residue with water (15 mL) and extract with EtOAc/hexanes (20 mL). Dry the organic layer over sodium sulfate, filter and concentrate. Purify the residue by flash chromatography (eluent CH2Cl2/hexanes 2/1) to give xxx mg (xx % yield) of the title compound.

1. temperatureheat
2. stirringwhile stirring at 50° C. for 20 minutes (min)
3. customheating at 60° C.
4. stirringstirring for 2 hours (h)
5. concentrationConcentrate the reaction mixture
6. customto remove DMF
7. washWash the residue with water (15 mL)
8. extractionextract with EtOAc/hexanes (20 mL)
9. dry with materialDry the organic layer over sodium sulfate
10. filtrationfilter
11. concentrationconcentrate
12. customPurify the residue by flash chromatography (eluent CH2Cl2/hexanes 2/1)