Sodium hydride → 3-Bromo-4-(cyclopropylmethoxy)pyridine

To a solution of 3-bromo-4-chloropyridine (CAN 36953-42-1, 8 g, 41.6 mmol) in dry DMF (100 ml) under argon atmosphere at room temperature were added cyclopropylmethanol (CAN 2516-33-8, 3.15 g, 3.45 ml, 43.6 mmol) and by portions sodium hydride 60% (1.75 g, 43.6 mmol). The resulting reaction was stirred at room temperature until gas evolution stopped. The reaction mixture was then stirred at 100° C. for 3 hours, cooled down to room temperature and quenched by addition of water. The reaction mixture was concentrated in vacuo. The residue was dissolved in ethylacetate and extracted with an aqueous solution 1.0M sodium bicarbonate. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient to yield the title compound (8.25 g, 87%) as a light yellow oil. MS (ESI, m/z): 228.2 (M+H+).

1. customThe resulting reaction
2. stirringThe reaction mixture was then stirred at 100° C. for 3 hours
3. temperaturecooled down to room temperature
4. customquenched by addition of water
5. concentrationThe reaction mixture was concentrated in vacuo
6. dissolutionThe residue was dissolved in ethylacetate
7. extractionextracted with an aqueous solution 1.0M sodium bicarbonate
8. customThe organic phase was collected
9. dry with materialdried over sodium sulfate
10. customevaporated down to dryness
11. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

ORD record

ord-a580daa25ba4441faf5ba899bf9f0da6

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409866B2