反应详情

温度

-10 °C

A solution of 2-hydroxy-2-difluoromethylpropionic acid (1.07 g, 7.65 mmol) in dry dimethylacetamide.(15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.91 g, 7.65 mmol) was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Aminobenzophenone (1.0 g, 5.1 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured into hydrochloric acid solution (1M) and extracted with ethyl acetate. The combined ethyl acetate fractions were washed with water and brine. After drying (Na2SO4) and decolorization (Charcoal) the solution was evaporated in vacuo. A off-white foam was obtained which was triturated with hexane/ethyl acetate. The crude product was filtered through a short silica gel column with chloroform and crystallized from chloroform/hexane to give the title tertiary carbinol (0.89 g, 55%) as shiny, buff-colored crystals; mp=123°-124° C. 1H-NMR (300 MHz, d6 -DMSO): 1.45 (s, 3H, CH3), 6.17 (t, J=55 Hz, 1H, CHF2), 6.77 (s, 1H, OH), 7.56 (t, 2H, ArH), 7.65-7.76 (m, 5H, ArH), 7.96 (d, J=8.7 Hz, 2H, ArH), 10.19 (s, 1H, NH). MS (CI, CH4): 320(M+1, 100). Analysis for C17H15F 2NO3.0.2 H2O: Calculated: C, 63.23; H, 4.81; N, 4.34 Found: C, 63.21; H, 4.74; N, 4.30

1. stirringto stir at -10° C. for 1 hour
2. stirringthe reaction mixture was stirred at -10° C. for a further 15 mins
3. temperatureto warm to room temperature where it
4. stirringwas stirred overnight
5. extractionextracted with ethyl acetate
6. washThe combined ethyl acetate fractions were washed with water and brine
7. dry with materialAfter drying (Na2SO4) and decolorization (Charcoal) the solution
8. customwas evaporated in vacuo
9. customA off-white foam was obtained which
10. customwas triturated with hexane/ethyl acetate
11. filtrationThe crude product was filtered through a short silica gel column with chloroform
12. customcrystallized from chloroform/hexane
13. customto give the title tertiary carbinol (0.89 g, 55%) as shiny, buff-colored crystals