Triethylamine → tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-fluoropiperidine-1-carboxylate

Temperature

70 °C

1-Hydroxybenzotriazole hydrate (114 mg, 0.845 mmol), WSC hydrochloride (162 mg, 0.845 mmol) and triethylamine (118 μL, 0.845 mmol) were added to a solution of tert-butyl cis(±)-4-amino-3-fluoropiperidine-1-carboxylate obtained in Example (196a) (123 mg, 0.564 mmol) and 4-chloro-5-ethyl-1H-imidazole 2-carboxylic acid obtained in Example (1d) (118 mg, 0.676 mmol) in DMA (3 mL) at room temperature, and the mixture was stirred at 70° C. for two hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and brine, and dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v) to obtain 159 mg of the title compound (75%) as a pale yellow foamy substance.

1. extractionfollowed by extraction with ethyl acetate
2. washThe resulting organic layer was washed with water and brine
3. dry with materialdried over anhydrous sodium sulfate
4. customthe insoluble matter was separated by filtration
5. concentrationThe filtrate was concentrated under reduced pressure
6. customthe resulting residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=1:1 v/v)

ORD record

ord-6f67f64169554502935eb7cdc2fac70e

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536197B2