Triethylamine → HCID 123789179, compound

Temperature

90 °C

To a solution of N-(tert-butoxycarbonyl)-D,L-alanine (3.49 g, 18.4 mmol) and triethylamine (2.56 mL, 18.4 mmol) in THF (100 mL) was added 2-methylpropyl chlorocarbonate (2.39 mL, 18.4 mmol) under ice-cooling, and the mixture was stirred for 30 min. To this solution was added 4-(benzyloxy)-2-nitroaniline (3.00 g, 12.3 mmol), and the mixture was heated under reflux at 90° C. for 16 hr under a nitrogen atmosphere. After being allowed to cool to room temperature, the reaction mixture was diluted with ethyl acetate, and the mixture was washed with 0.5N hydrochloric acid, 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. This solution was applied to basic silica gel column chromatography (ethyl acetate). The solvent was evaporated under reduced pressure to give tert-butyl (2-{[4-(benzyloxy)-2-nitrophenyl]amino}-1-methyl-2-oxoethyl)carbamate (5.10 g) as a crude product. To a solution (66 mL) of the obtained oil (5.10 g, 12.3 mmol) in 90% aqueous acetic acid was slowly added zinc powder (8.03 g, 123 mmol) under ice-cooling, and the mixture was stirred for 30 min. The reaction mixture was filtered through celite, and the filtrate was stirred under heating at 70° C. for 2 hr. The reaction mixture was allowed to cool to room temperature, and the solvent was evaporated under reduced pressure. The obtained residue was diluted with ethyl acetate, and the mixture was washed with 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solution was applied to basic silica gel column chromatography (ethyl acetate), and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate), and triturated with diisopropyl ether to give the title compound (663 mg, yield in 3 steps 15%).

1. temperaturecooling
2. temperaturethe mixture was heated
3. temperatureto cool to room temperature
4. washthe mixture was washed with 0.5N hydrochloric acid, 10% aqueous potassium carbonate solution and saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customThe solvent was evaporated under reduced pressure

ORD record

ord-1ef5b72456b14b3489fc8afa94414761

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501804B2