Dimethylformamide → HCID 67240591, compound

Temperature

100 °C

A 350 mL sealable flask was charged with (R)-2′-amino-3-bromo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-7-ol (12.10 g, 34.8 mmol) and DMF (99 mL, 34.8 mmol). To this solution was added cesium carbonate (28.3 g, 87 mmol). The resulting brown slurry was stirred at rt for 3 minutes before neopentyl iodide (9.21 mL, 69.5 mmol) was added in one portion. The reaction vessel was sealed and heated at 100° C. After heating for 4 hours another 1 mL of neopentyl iodide was added and heating at 100° C. was continued for another 1 hour at which point the reaction was allowed to cool to room temperature. The reaction was diluted with ethyl acetate (500 mL) and poured into water (2000 mL) before being transferred into a separatory funnel containing ethyl acetate (500 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×500 mL). The combined organic layers were washed with water and then brine. The aqeuous layer was combined with the above brined wash and was then extracted with DCM (2×500 mL). The organic layers were washed with water and then brine. All of the organigs were combined, 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), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (R)-3-bromo-7-(neopentyloxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a light yellow solid.

1. additionwas added in one portion
2. customThe reaction vessel was sealed
3. additionwas added
4. temperatureheating at 100° C.
5. temperatureto cool to room temperature
6. custombefore being transferred into a separatory funnel
7. customThe layers were separated
8. extractionthe aqueous layer was extracted with ethyl acetate (3×500 mL)
9. washThe combined organic layers were washed with water
10. washbrined wash
11. extractionwas then extracted with DCM (2×500 mL)
12. washThe organic layers were washed with water
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customto provide a brown foam that
17. customwas purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (330 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide)

ORD record

ord-0c401eb711354430af6f8ed82586a401

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426447B2