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, 1.00 equiv) in ether (60 mL)-30° C. was added dropwise a solution of BF3.Et2O (16.0 mL, 1.30 equiv) in ether (20 mL). After stirring 30 min at −30° C., a solution of ethyl 2-diazoacetate (16.0 g, 140 mmol, 1.30 equiv) in ether (20 mL) was added dropwise to the reaction at −30° C. The resulting solution was stirred for 1 h at −30° C., then warmed to 25° C. and stirred for 2 h. The reaction was then quenched with 100 mL of 30% aqueous potassium carbonate. The resulting mixture was extracted with 2×250 mL of ethyl acetate, and the combined organic layers were washed with 2×50 mL of brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1/10) as eluent to furnish 19.0 g (66%) of the title compound as a light yellow oil.

1. stirringThe resulting solution was stirred for 1 h at −30° C.
2. temperaturewarmed to 25° C.
3. stirringstirred for 2 h
4. customThe reaction was then quenched with 100 mL of 30% aqueous potassium carbonate
5. extractionThe resulting mixture was extracted with 2×250 mL of ethyl acetate
6. washthe combined organic layers were washed with 2×50 mL of brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1/10) as eluent

ORD record

ord-beebc2b6096945e3ae7c3cb8e1b60665

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871790B2