Hydrochloric Acid → 4,4-Difluoro-1-[5-chloro-2-thienyl]-butane-1,3-dione

Ethyl difluoroacetate (3.51 g, 28.3 mmol) was placed in a 100 mL round bottom flask and dissolved in ether (10 mL). To the stirred solution was added 25 weight % sodium methoxide (6.12 g, 28.3 mmol) followed by 2-acetyl-5-chlorothiophene (4.12 g, 25.6 mmol). A pink precipitate formed after 5 minutes which was dissolved by adding ether (10 mL) and THF (10 mL) to the reaction. The reaction was stirred at room temperature overnight (15.75 hours), then treated with 3N HCl (15 mL). The organic layer was collected and washed with brine (20 mL), dried over MgSO4, and concentrated in vacuo to give a red solid (5.94 g) which was recrystallized from methylene chloride/isooctane to give the diketone as a yellow solid (2.02 g, mp 72°-77° C., 33%). 1H NMR (CDCl3) 300 MHz 14.60 (br s, 1H) , 7.57 (d, J=4.2 Hz, 1H), 7.01 (d, J=4.2 Hz, 1H), 6.32 (s, 1H), 6.04 (t, J=54.2 Hz, 1H); 19F NMR (CDCl3) 300 MHz: -127.01 (d); M+ 238.

1. customA pink precipitate formed after 5 minutes which
2. dissolutionwas dissolved
3. customto the reaction
4. customThe organic layer was collected
5. washwashed with brine (20 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo

ORD record

ord-95843e4d2c114a02a93d7cd510537131

Source dataset

uspto-grants-1996_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05521207