Benzyl Alcohol → HCID 58980614, compound

Temperature

0 °C

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.

1. temperaturethen warmed to room temperature
2. stirringstirred an additional 0.5 h
3. stirringthe resultant slurry was stirred at room temperature for 1 h
4. extractionthe aqueous phase was extracted with methylene chloride
5. additionToluene (2 mL) was added to the combined extracts which
6. dry with materialwere subsequently dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo to a volume of 1 mL (Caution was taken to avoid complete concentration)
9. temperaturethe mixture was refluxed an additional 1.5 h
10. concentrationConcentration in vacuo
11. filtrationfollowed by filtration of the residue through a plug of silica-gel with diethyl ether
12. customprovided the crude Cbz-protected aniline
13. additionwas added
14. stirringshaken at room temperature for 0.25 h
15. filtrationThe solution was then filtered through diatomaceous earth
16. concentrationconcentrated
17. customthe residue was purified by silica-gel chromatography (ethyl acetate)

ORD record

ord-085790732d7240c189880e5bf4a6efd4

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592332B2