HCID 57433608, compound → 6-(4-Fluorophenyl)-imidazo[2,1-b]oxazole

Temperature

-10 °C

The 1-(4-fluorophenyl)-2-(2-iminooxazol-3-yl)-ethanone hydrobromide salt (10.0 g, 0.32 mol) was introduced in a two-neck flask, fitted with a condenser, and flushed with nitrogen. Anhydrous toluene (100 ml) was added and the mixture was cooled to −10° C. TiCl4 (17.5 ml, 0.16 mol) was added over a period of 30 minutes. The reaction becomes deep red and a dark precipitate was formed. The reaction mixture was allowed to warm to room temperature. The mixture was then brought to reflux and kept a reflux for 5.5 hrs. The reaction mixture was cooled to room temperature overnight. The toluene was decanted and iced water (60 ml) was added to the residue (caution!), which turned from dark brown to beige. The resulting suspension was transferred to a large beaker and treated with saturated aqueous sodium carbonate solution until pH 8. A saturated aqueous sodium chloride solution was added (200 ml), followed by 600 ml of ethyl acetate and the mixture was stirred vigorously for one hour. The organic phase was separated and the aqueous phase was further extracted with two portions of 600 ml of ethyl acetate. The organic extracts were dried over sodium sulfate and concentrated in vacuo, yielding 6.84 g of a pale yellow solid. 400 MHz 1H NMR (CDCl3) δ: 7.78-7.72 (m, 2H), 7.37 (d, J=1.8 Hz, 1), 7.31 (d, J=1.8 Hz, 1), 7.24 (s, 1H), 7.10-7.00 (m, 2H).

1. customfitted with a condenser
2. customflushed with nitrogen
3. additionAnhydrous toluene (100 ml) was added
4. customa dark precipitate was formed
5. temperatureto warm to room temperature
6. temperatureto reflux
7. temperaturea reflux for 5.5 hrs
8. temperatureThe reaction mixture was cooled to room temperature overnight
9. customThe toluene was decanted
10. additioniced water (60 ml) was added to the residue (caution!), which
11. additiontreated with saturated aqueous sodium carbonate solution until pH 8
12. additionA saturated aqueous sodium chloride solution was added (200 ml)
13. customThe organic phase was separated
14. extractionthe aqueous phase was further extracted with two portions of 600 ml of ethyl acetate
15. dry with materialThe organic extracts were dried over sodium sulfate
16. concentrationconcentrated in vacuo

ORD record

ord-5527e0450a5544249024ffb86820fa8c

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07501430B2