Benzyl Alcohol → HCID 58980614, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl chloroformate (101 microL, 1.05 mmol) was added dropwise to a solution of the above acid (200 mg, 0.96 mmol) and N,N-diisopropylethylamine (183 microL, 1.05 mmol) in acetone (1.0 mL) at 0° C. The mixture was stirred for 0.5 h at 0° C. then warmed to room temperature and stirred an additional 0.5 h. Lastly, a solution of sodium azide (5.0 M in water, 400 μL, 2.00 mmol) was added and the resultant slurry was stirred at room temperature for 1 h. Water was added to the reaction mixture and the aqueous phase was extracted with methylene chloride. Toluene (2 mL) was added to the combined extracts which were subsequently dried over sodium sulfate, filtered, and concentrated in vacuo to a volume of 1 mL (Caution was taken to avoid complete concentration). The resultant toluene solution of the acyl azide was then added dropwise to a refluxing solution of benzyl alcohol (120 microL, 1.15 mmol) in toluene (1 mL) and the mixture was refluxed an additional 1.5 h. Concentration in vacuo, followed by filtration of the residue through a plug of silica-gel with diethyl ether provided the crude Cbz-protected aniline. This crude product was immediately dissolved in ethanol/water (10:1, 3.0 mL) in a Parr hydrogenation vessel and Pd(OH)2 (20% on carbon, 20 mg) was added. The reaction was placed under a hydrogen atmosphere (50 psi) and shaken at room temperature for 0.25 h. The solution was then filtered through diatomaceous earth, concentrated and the residue was purified by silica-gel chromatography (ethyl acetate) to provide 2-tert-butyl-5-methoxy-pyridin-4-ylamine (95 mg, 56%) as a white solid.

Provenance & Evidence