Dimethylformamide → 3-Chlorobicyclo[2.2.1]hept-2-ene-2-carbaldehyde

Temperature

0 °C

A 250-mL three-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was purged with nitrogen and charged with anhydrous 1,2-dichloroethane (24 mL) and anhydrous DMF (9.12 g, 125 mmol). The reaction mixture was cooled to 0° C. and phosphorus oxychloride (15.3 g, 100 mmol) was added over a period of 5 minutes while maintaining the reaction temperature between 0 and 10° C. The cooling bath was removed and the reaction was stirred at room temperature for 30 minutes. A solution of bicyclo[2.2.1]heptan-2-one (5.50 g, 50.0 mmol) in 1,2-dichloroethane (10 mL) was added and the resulting mixture was heated at 80° C. overnight. After this time, the reaction was poured into a solution of potassium monohydrogen phosphate (43.5 g, 250 mmol) in water (200 mL) and stirred for 15 minutes. The organic layer was separated and concentrated under reduced pressure. The residue was dissolved in methylene chloride (300 mL) and washed with water (2×50 mL). The methylene chloride layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:100 ethyl acetate/petroleum ether to afford 167a as a yellow oil (2.2 g, 28%). MS: [M+H]+ 157. 1H NMR (500 MHz, CDCl3) δ 9.80 (s, 1H), 3.42-3.41 (m, 1H), 3.08-3.07 (m, 1H), 1.95-1.77 (m, 2H), 1.68-1.66 (m, 1H), 1.41-1.17 (m, 3H).

1. customA 250-mL three-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
2. customwas purged with nitrogen
3. temperaturewhile maintaining the reaction temperature between 0 and 10° C
4. customThe cooling bath was removed
5. temperaturethe resulting mixture was heated at 80° C. overnight
6. stirringstirred for 15 minutes
7. customThe organic layer was separated
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in methylene chloride (300 mL)
10. washwashed with water (2×50 mL)
11. dry with materialThe methylene chloride layer was dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by silica-gel column chromatography
15. washeluting with 1:100 ethyl acetate/petroleum ether

ORD record

ord-342d1c7a6b394ed79cf45b1f1c94a3bd

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238655B2