Diethyl Ether → 2-Cyclopropanecarbonylpyridine

Dry magnesium powder (0.79 g, 32.6 mmol), which had been previously crushed in a mortar with a pestle, was charged into a dry round bottom flask under a nitrogen atmosphere. To this was added diethyl ether (20 mL), followed by bromocyclopropane (3.95 g, 2.61 mL, 32.6 mmol). A small amount of iodine (0.002 g) was added to initiate formation of the Grignard reagent. The reaction was heated to a gentle reflux for a short period of time (˜1 h) until all of the magnesium metal had reacted. The material was allowed to stir at room temperature for 2 hours, and then cooled in an ice bath. To this was added 2-cyanopyridine (2.0 g, 19.2 mmol) in diethyl ether (10 mL). The mixture was stirred for 3 hours, and then carefully quenched with sat. ammonium chloride (3 mL). The reaction was then acidified with 15% aq. hydrochloric acid (3 mL). The mixture was stirred for 20 minutes, and then made basic by the addition of 10 N sodium hydroxide until the pH was approximately 9. To this solution was added ethyl acetate (300 mL), and the aqueous layer was extracted with water (30 mL). The organic layer was washed with brine, dried over Na2SO4 and evaporated to dryness giving a yellow oil. This oil was chromatographed (SiO2, hexanes/ethyl acetate: 75/25) to give the title compound as a yellow oil (1.48 g, 52%). 1H NMR (300 MHz, DMSO-d6): δ 1.10 (m, 4H); 3.46 (m, 1H); 7.70 (m, 1H); 7.96 (t, 1H, J=78. Hz); 8.01 (t, 1H, J=7.8 Hz); 8.77 (d, 1H, J=4.8 Hz).

1. additionwas charged into a dry round bottom flask under a nitrogen atmosphere
2. temperatureThe reaction was heated to
3. customhad reacted
4. temperaturecooled in an ice bath
5. stirringThe mixture was stirred for 3 hours
6. customcarefully quenched with sat. ammonium chloride (3 mL)
7. stirringThe mixture was stirred for 20 minutes
8. additionmade basic by the addition of 10 N sodium hydroxide until the pH was approximately 9
9. additionTo this solution was added ethyl acetate (300 mL)
10. extractionthe aqueous layer was extracted with water (30 mL)
11. washThe organic layer was washed with brine
12. dry with materialdried over Na2SO4
13. customevaporated to dryness
14. customgiving a yellow oil
15. customThis oil was chromatographed (SiO2, hexanes/ethyl acetate: 75/25)

ORD record

ord-ab5c28ad30f2406bbd7b44ec96c71092

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946463B2