Sodium hydride → 1-Tert-butyl 4-ethyl 4-fluoro-5-oxoazepane-1,4-dicarboxylate

Temperature

0 °C

NaH (2.66 g, 105 mmol) was suspended in THF (300 mL) and cooled to 0° C., and 1-tert-butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate (30 g, 105 mmol) was added as THF solution (550 mL) using an addition funnel over 30 minutes. The mixture was stirred for 30 minutes and then diluted with DMF (200 mL). Selectfluor (41.0 g, 116 mmol) was added as a DMF solution (200 mL). The mixture was warmed to ambient temperature and stirred for 2 hours. The mixture was then concentrated to remove THF and diluted with 1N KHSO4 (300 mL), water (300 mL) and EtOAc (750 mL). The organic layer was washed with brine (2×250 mL). The combined aqueous layers were washed with EtOAc (200 mL) and this organic layer was washed with brine (200 mL). The combined organic layers were then dried over Na2SO4, filtered and concentrated. The crude product was passed through a silica gel plug (1 kg, 20 to 40% EtOAc/hexanes) to provide 23.6 g (74%) of the product as a colorless oil.

1. customover 30 minutes
2. temperatureThe mixture was warmed to ambient temperature
3. stirringstirred for 2 hours
4. concentrationThe mixture was then concentrated
5. customto remove THF
6. additiondiluted with 1N KHSO4 (300 mL), water (300 mL) and EtOAc (750 mL)
7. washThe organic layer was washed with brine (2×250 mL)
8. washThe combined aqueous layers were washed with EtOAc (200 mL)
9. washthis organic layer was washed with brine (200 mL)
10. dry with materialThe combined organic layers were then dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-6911c5dfee16448994fa46c7ad128415

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2