Dimethylformamide → 2,3-Dichloropyridine-4-carbaldehyde

Temperature

-78 °C

To a solution of 2,3-dichloropyridine (10 g, 67.57 mmol) [C.A.S. 2402-77-9] in dry THF (200 ml) cooled at −78° C. under a nitrogen atmosphere, n-butyllithium (37.165 ml, 74 mmol, 2 M in hexanes) was dropwise added. The resulting reaction mixture was stirred at −78° C. for 20 min. Then dry DMF (6.28 ml, 81.087 mmol) was added dropwise. After 15 min stirring at −78° C., the mixture was allowed to warm to room temperature, quenched with water and extracted with DCM. The combined organic extracts were dried (Na2SO4) and evaporated in vacuo. The crude residue was purified by short open column chromatography (DCM as eluent). The desired product fractions were collected and evaporated in vacuo to give a residue that was further purified by column chromatography (silica gel; DCM/heptane up to 50% as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate compound D41 (4.15 g, 34.9%) as a white solid.

1. customThe resulting reaction mixture
2. stirringAfter 15 min stirring at −78° C.
3. temperatureto warm to room temperature
4. customquenched with water
5. extractionextracted with DCM
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. customevaporated in vacuo
8. customThe crude residue was purified by short open column chromatography (DCM as eluent)
9. customThe desired product fractions were collected
10. customevaporated in vacuo
11. customto give a residue that
12. customwas further purified by column chromatography (silica gel; DCM/heptane up to 50% as eluent)
13. customThe desired fractions were collected
14. customevaporated in vacuo
15. customto yield intermediate compound

ORD record

ord-bac72307b2ce46d4b960e36c95ec9d67

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785486B2