Boron trifluoride etherate → 1-tert-Butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate

Temperature

-30 °C

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (20.0 g, 100 mmol) in diethylether (60 mL) under nitrogen at −30° C., was added drop-wise a solution of BF3.Et2O (16.0 mL, 130 mmol) in ether (20 mL). After stirring for 30 min at −30° C., a solution of ethyl 2-diazoacetate (16.0 g, 140 mmol) in ether (20 mL) was added drop-wise to the reaction at −30° C. The resulting solution was stirred for 1 h at −30° C., then at room temperature for 2 h. The reaction was carefully quenched with 30% aqueous potassium carbonate (100 mL) and the resulting mixture was extracted with ethyl acetate (2×250 mL). The combined organic extracts were washed with brine (2×50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/10) as the eluent to furnish 19 g (66%) of the title compound as a light yellow oil.

1. customto the reaction at −30° C
2. stirringThe resulting solution was stirred for 1 h at −30° C.
3. waitat room temperature for 2 h
4. customThe reaction was carefully quenched with 30% aqueous potassium carbonate (100 mL)
5. extractionthe resulting mixture was extracted with ethyl acetate (2×250 mL)
6. washThe combined organic extracts were washed with brine (2×50 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/10) as the eluent

ORD record

ord-748e6d0fc6b44606a092eb8077d78e66

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428502B2