Cyclobutanone → HCID 90203880, compound

Temperature

-15 °C

To a solution of 3-bromo-4-chloropyridine (CAN 36953-42-1, 1 g, 5.2 mmol) in dry THF (25.0 ml) cooled down to −15° C. under an argon atmosphere was added isopropyl magnesium chloride, lithium chloride complex 1.3M solution in THF (4.2 ml, 5.46 mmol) and the reaction mixture was stirred at −15° C. for 1 hour. To the reaction mixture at −15° C. was slowly added cyclobutanone (CAN 1191-95-3, 401 mg, 428 μl, 5.72 mmol) and the reaction was stirred at −15° C. for 2 hours. The reaction was then let to warm up to 0° C. and stirred at 0° C. for 2 hours. Reaction was quenched by addition of water and the reaction mixture was concentrated in vacuo. The residue was dissolved in ethylacetate and extraction with an 3.0M aqueous solution of ammonium chloride. The organic phase was 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 (832 mg, 78%) as a yellow oil. MS (ESI, m/z): 184.3 (MH+).

1. customat −15° C.
2. stirringthe reaction was stirred at −15° C. for 2 hours
3. temperatureto warm up to 0° C.
4. stirringstirred at 0° C. for 2 hours
5. customReaction
6. customwas quenched by addition of water
7. concentrationthe reaction mixture was concentrated in vacuo
8. dissolutionThe residue was dissolved in ethylacetate
9. extractionextraction with an 3.0M aqueous solution of ammonium chloride
10. dry with materialThe organic phase was dried over sodium sulfate
11. customevaporated down to dryness
12. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethylacetate gradient

ORD record

ord-d9d8b77f14174713b64c2dad86f2bcf6

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409866B2