Water → 1-Tert-butyl 4-ethyl 6-methyl-5-oxoazepane-1,4-dicarboxylate

Temperature

-78 °C

To 2 g (7.01 mmol) 5-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (route 1 step a) in 25 mL anhydrous THF at −78° C. was added 9.7 mL (17.46 mmol) of a 1.8 M solution of lithium diisopropylamide in heptane/THF dropwise under an atmosphere of nitrogen. The reaction mixture was stirred at −78° C. for 30 minutes and then warmed up to 0° C. 0.48 mL (7.70 mmol) iodomethane was added at 0° C. and the reaction was left to warm up to room temperature over a period of 2 hours. 100 mL of H2O was added and the mixture was extracted with EtOAc (3×100 mL), the organic layers were combined, washed with H2O (2×100 mL) and saturated brine (100 mL) and dried over MgSO4. After filtration and evaporation of the solvent the product was purified by column chromatography (silica, hexane/EtOAc 9:1).

1. temperaturewarmed up to 0° C
2. waitthe reaction was left
3. temperatureto warm up to room temperature over a period of 2 hours
4. extractionthe mixture was extracted with EtOAc (3×100 mL)
5. washwashed with H2O (2×100 mL) and saturated brine (100 mL)
6. dry with materialdried over MgSO4
7. filtrationAfter filtration and evaporation of the solvent the product
8. customwas purified by column chromatography (silica, hexane/EtOAc 9:1)

ORD record

ord-b3143536b5b645d3a748b967fee8105f

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346816B2