Imidazole → HCID 57781089, compound

Temperature

70 °C

A flask is charged with polymer-supported triphenylphosphine (1.48 mmol/g, 6.87 g, 10.17 mmol) and dichloromethane (70 mL). Bromine (1.58 g, 9.77 mmol) is added at r.t., followed with N,N-diethyl-3,4-difluoro-2-hydroxymethyl-benzamide (1.100 g, 4.070 mmol) in dichloromethane (15 mL). After 5 min, the mixture is filtered and the resin is washed several times with dichloromethane. The resulting filtrate is concentrated in vacuo to yield an oil. Imidazole (2.80 g, 40.70 mmol) is added, followed with acetonitrile (30 mL) and the mixture is heated to 70° C. After 5 min at 70° C., the mixture is allowed to cool down, diluted with ethyl acetate and extracted three times with 1M aqueous HCl. The combined aqueous phase is washed once with dichloromethane. The aqueous phase is then cooled to 0° C. and the pH is adjusted to 12 with cold 4M aqueous NaOH. The aqueous phase is then extracted with dichloromethane. The combined extraction fractions are dried over MgSO4 and filtered. The sample is concentrated in vacuo, taken up in ethyl acetate and washed with water (three times), and brine. The organic phase is dried over MgSO4, filtered and concentrated in vacuo to give N,N-diethyl-3,4-difluoro-2-imidazol-1-ylmethyl-benzamide as a yellow oil; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.95 (t, J=7.1 Hz, 3 H), 1.26 (t, J=7.1 Hz, 3 H), 2.82 (q, J=7.1 Hz, 2 H), 3.52 (q, J=7.1 Hz, 2 H), 5.25 (br. s., 2 H), 6.96 (s, 1 H), 6.98-7.03 (m, 1 H), 7.01 (s, 1 H), 7.16-7.25 (m, 1 H), 7.51 (s, 1 H).

1. filtrationthe mixture is filtered
2. washthe resin is washed several times with dichloromethane
3. concentrationThe resulting filtrate is concentrated in vacuo
4. customto yield an oil
5. waitAfter 5 min at 70° C.
6. temperatureto cool down
7. extractionextracted three times with 1M aqueous HCl
8. washThe combined aqueous phase is washed once with dichloromethane
9. temperatureThe aqueous phase is then cooled to 0° C.
10. extractionThe aqueous phase is then extracted with dichloromethane
11. extractionThe combined extraction fractions
12. dry with materialare dried over MgSO4
13. filtrationfiltered
14. concentrationThe sample is concentrated in vacuo
15. washwashed with water (three times), and brine
16. dry with materialThe organic phase is dried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated in vacuo

ORD record

ord-7978acdeef3b4ac9a25f35eadc827e38

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153674B2