Hydrochloric Acid → 1-(5-Bromothiophen-2-yl)-4,4-difluorobutane-1,3-dione

Ethyl difluoroacetate (2.43 g, 19.6 mmol) was placed in a 100 mL round bottom flask, and dissolved in ether (15 mL). To the stirred solution was added 25 weight % sodium methoxide (4.23 g, 19.5 mmol) followed by 2-acetyl-5-bromothiophene (3.59 g, 17.5 mmol). After two hours a precipitate formed and THF (15 mL) was added to allow stirring to continue. The reaction was stirred at room temperature 6.2 hours, then treated with 3N HCl (20 mL). The organic layer was collected and washed with brine, dried over MgSO4, and concentrated in vacuo to give a yellow oil which was crystallized from methylene chloride/isooctane to give yellow needles (3.63 g, mp 83.5°-85° C., 73% ). 1H NMR (CDCl3) 300 MHz 14.60 (br s, 1H), 7.53 (d, J=4.0 Hz, 1H), 7.15 (d, J=4.0 Hz, 1H), 7.19 (m, 1H), 6.32 (s, 1H), 6.04 (t, J=54.2 Hz, 1H); 19F NMR (CDCl3) 300 MHz: -127.00 (d) ; M+282.

1. customAfter two hours a precipitate formed
2. stirringThe reaction was stirred at room temperature 6.2 hours
3. customThe organic layer was collected
4. washwashed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customto give a yellow oil which
8. customwas crystallized from methylene chloride/isooctane

ORD record

ord-ab8018c562ad443086ff6756f78cd16c

Source dataset

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05466823