Dimethyl Sulfoxide → (S)-7-bromo-3-(neopentyloxy)-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

A vial was charged with 2,2-dimethylpropan-1-ol (100 mg, 1.130 mmol) and DMSO (1130 μL) to give a clear solution. Sodium hydride (60% in mineral oil; 45.2 mg, 1.130 mmol) was added and the vial was placed in a 100° C. oil bath for 5 min, then was removed from the heat and cooled to RT. (S)-7-bromo-3-chloro-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (Intermediate 1B, 86 mg, 0.226 mmol) was added to give an orange solution. The vial was sealed and heated in a 100° C. oil bath for 2 h. The mixture was cooled to room temperature, then diluted with water and EtOAc. Brine was added and the layers were separated. The aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (0-100% EtOAc/Hexane) to give (S)-7-bromo-3-(neopentyloxy)-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a light-yellow solid.

1. customto give a clear solution
2. customwas placed in a 100° C.
3. customfor 5 min
4. customwas removed from the
5. temperatureheat
6. customto give an orange solution
7. customThe vial was sealed
8. temperatureheated in a 100° C. oil bath for 2 h
9. temperatureThe mixture was cooled to room temperature
10. customthe layers were separated
11. extractionThe aq. layer was extracted with EtOAc (2×)
12. dry with materialThe combined organic extracts were dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated
15. customThe residue was purified by chromatography on silica gel (0-100% EtOAc/Hexane)

ORDレコード

ord-1b46f17c96ab489198e19403da21534c

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08497264B2