反应详情

Into a 250 mL round bottom flask was weighed 2.3 g of crude 2-(1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)acetonitrile (8.0 mmol). To this was added 40 mL of ethanol and 2.5 g of KOH (44 mmol). The resulting mixture was heated to reflux. After 17 hours at reflux the reaction was cooled and concentrated in vacuo to remove most of the ethanol. The resulting dark oil was taken up in H2O and EtOAc and acidified by the addition of 3N aqueous HCl. The acidic aqueous was extracted with EtOAc (3×), the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford the crude acid as a dark oil. The crude product was purified by silica gel flash chromatography on an 80 g column using gradient elution from 0% to 40% acetonitrile/CH2Cl2 and collected by monitoring the UV response at 240 nm. Appropriate fractions were combined and concentrated in vacuo to afford 2-(1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)acetic acid as a dark glass. The product was not completely pure and was taken up in 1N NaOH and Et2O. The ether layer was extracted with 1N NaOH (1×) and the combined basic aqueous layers were extracted with Et2O (1×). The basic layer was acidified by the addition of concentrated HCl and was extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford 2-(1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)acetic acid as a yellow oil that partially solidified after standing under vacuum overnight: yield 1.5 g (61% yield); 1H NMR (400 MHz, CDCl3): δ 7.58-7.54 (m, 1H), 7.52-7.39 (m, 3H), 6.73 (s, 1H), 3.80-3.45 (broad hump, 2H); MS (ESI) m/z 305.0 [M+H]+.

1. customInto a 250 mL round bottom flask was weighed
2. temperatureThe resulting mixture was heated to reflux
3. temperatureAfter 17 hours at reflux the reaction
4. temperaturewas cooled
5. concentrationconcentrated in vacuo
6. customto remove most of the ethanol
7. additionEtOAc and acidified by the addition of 3N aqueous HCl
8. extractionThe acidic aqueous was extracted with EtOAc (3×)
9. washthe combined organic extracts were washed with brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto afford the crude acid as a dark oil
14. customThe crude product was purified by silica gel flash chromatography on an 80 g column
15. washelution from 0% to 40% acetonitrile/CH2Cl2
16. customcollected
17. concentrationconcentrated in vacuo