反应详情

A vial was charged with neopentyl alcohol (0.579 g, 6.57 mmol) and DMF (6.57 mL). Sodium hydride (60% in mineral oil; 0.263 g, 6.57 mmol) was added and the reaction was stirred for 10 minutes at room temperature. The vial was heated to 100° C. for 5 min. The vial was cooled to rt. (S)-7-bromo-3-chloro-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (0.500 g, 1.314 mmol) was added in one portion. The vial was sealed and heated to 100° C. three hours. The mixture was diluted with ethyl acetate and water. A small amount of brine was added and the layers were separated. The aq. layer was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (0-100% EtOAc/Hexanes) to give 175 mg of (S)—N-(7-bromo-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazine]-5′-yl)formamide as a light yellow solid.

1. temperatureThe vial was heated to 100° C. for 5 min
2. temperatureThe vial was cooled to rt
3. customThe vial was sealed
4. temperatureheated to 100° C. three hours
5. customthe layers were separated
6. extractionThe aq. layer was extracted twice with ethyl acetate
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by chromatography (0-100% EtOAc/Hexanes)