反应详情

温度

70 °C

A sealable tube was charged with (S)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (3.00 g, 8.62 mmol), tetrakis(triphenylphosphine)palladium (0.996 g, 0.862 mmol), copper(i) iodide (0.164 g, 0.862 mmol). To this was added trimethyl((3-methyloxetan-3-yl)ethynyl)silane (2.90 g, 17.23 mmol) followed by tetra-n-butylammonium fluoride (1 M in THF) (25.9 mL, 25.9 mmol). The resulting brown solution was flushed with argon and heated at 70° C. for 5 hours. The reaction was cooled to rt and diluted with 250 mL of water. The slurry was poured into a separatory funnel containing EtOAc (500 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×250 mL). In the first extraction a slight emulsion formed, this was cleared upon the addition of 50 mL of brine. The aqueous layer was then extracted with CH2Cl2 (3×200 mL). The organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown foam that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-2′-amino-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol as a brown foam.

1. customThe resulting brown solution was flushed with argon
2. temperatureThe reaction was cooled to rt
3. additiondiluted with 250 mL of water
4. additionThe slurry was poured into a separatory funnel
5. additioncontaining EtOAc (500 mL)
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with EtOAc (3×250 mL)
8. extractionIn the first extraction a slight emulsion
9. customformed
10. extractionThe aqueous layer was then extracted with CH2Cl2 (3×200 mL)
11. washThe organic layers were washed with brine
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto provide a brown foam that
16. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-100% CH2Cl2 to 10:1 methanol in methylenechloride with 0.1% ammonium hydroxide)