Diisobutylaluminum hydride → tert-Butyl (4-(2-hydroxyethyl)pyridin-2-yl)carbamate

Temperature

-69 °C

To a solution of ethyl 2-(2-(tert-butoxycarbonylamino)pyridin-4-yl)acetate (WO 2007089512) (10.0 g, 35.7 mmol) under N2 in THF (100 mL), at −78° C., was added a solution of DIBAL in THF (1.0M, 71.0 mL, 71.0 mmol) over 1 hr. The reaction mixture was stirred at −78 to −60° C. for 40 min and was then warmed to −15° C. over 1 hr. The solution was re-cooled to −78° C. and was treated with a further aliquot of DIBAL solution (36.0 mL, 36.0 mmol) and was allowed to warm to −40° C. and stirred for 1 hr. The reaction was quenched by the cautious addition of water (10 mL), followed MgSO4. The solids were removed by filtration and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in hexanes, 65% v/v, isocratic elution) to give tert-butyl 4-(2-hydroxyethyl)pyridin-2-ylcarbamate, (6.0 g, 64%) as a yellow solid: m/z 239 (M+H)+ (ES+).

1. temperaturewas then warmed to −15° C. over 1 hr
2. temperatureThe solution was re-cooled to −78° C.
3. temperatureto warm to −40° C.
4. stirringstirred for 1 hr
5. customThe reaction was quenched by the cautious addition of water (10 mL)
6. customThe solids were removed by filtration
7. customthe filtrate was evaporated in vacuo
8. customThe residue was purified by flash column chromatography (SiO2, 330 g, EtOAc in hexanes, 65% v/v, isocratic elution)

ORD record

ord-55b4d000d50842e994804ae90d842bee

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260410B2