4-(Boc-amino)pyridine → tert-butyl N-[3-(2-hydroxyethyl)pyridin-4-yl]carbamate

Temperature

-78 °C

Solution A was prepared by combining pyridin-4-yl-carbamic acid tert-butyl ester (388 mg, 2 mmol) in THF (5 mL) and cooling to −78° C. t-BuLi (2.8 mL, 1.7M solution in pentane) was added dropwise. Once the addition was complete, the solution was stirred at −78° C. for 15 minutes, then warmed to −15° C. and stirred for 90 minutes. In a separate flask, solution B was prepared by combining bromoethanol (0.21 mL, 3 mmol) in THF (5 mL) and cooling to −78° C. n-BuLi (1.44 mL, 2.5M solution in hexanes) was added dropwise. Once the addition was complete, the solution was stirred at −78° C. for 10 minutes. Solution A was recooled to −78° C., and solution B was added to solution A via cannula. Stirred with warming to room temperature for 2 hours. The reaction was recooled, and quenched with water. Partitioned between CH2Cl2 and water. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 100% ethyl acetate to provide 91 mg (19%) of [3-(2-hydroxy-ethyl)-pyridin-4-yl]-carbamic acid tert-butyl ester.

1. customSolution A was prepared
2. additionwas added dropwise
3. additionOnce the addition
4. temperaturewarmed to −15° C.
5. stirringstirred for 90 minutes
6. additionwas added dropwise
7. additionOnce the addition
8. stirringthe solution was stirred at −78° C. for 10 minutes
9. customwas recooled to −78° C.
10. stirringStirred
11. temperaturewith warming to room temperature for 2 hours
12. customquenched with water
13. customPartitioned between CH2Cl2 and water
14. washThe organic layer was washed with brine
15. dry with materialdried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated under vacuum
18. customThe residue was purified by flash column chromatography on silica gel with 100% ethyl acetate

ORD record

ord-35cea2680c134738a9e99f915b2e684b

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456169B2