反应详情

To a slurry of 4-amino-2-(trifluoromethyl)benzonitrile (30.09 g, 162 mmol) and NaBH3CN (21.35 g, 340 mmol) in CH2Cl2 (160 mL) at ice bath temperature neat TFA (160 mL, 2.08 mol) was added dropwise at a rate such that the internal temperature remained below 5° C. (CAUTION: exothermic reaction with hydrogen gas evolution). Trifluoroacetaldehyde hydrate (52.2 g, 405 mmol) was then added over 5 min (CAUTION: slightly exothermic reaction, with gas evolution). After 41 h, the mixture was slowly poured into sat'd NaHCO3 (1 L) at 0° C. The mixture was then completely neutralized by portionwise addition of solid NaHCO3. The mixture was stirred 30 min and precipitated solids were collected by filtration. Organic and aqueous phases of the filtrate were separated, and the aqueous layer extracted with CH2Cl2 (3×150 mL). Combined organic extracts were concentrated to dryness, combined with the solids collected previously, dissolved in EtOAc, washed (H2O, brine), dried over Na2SO4, filtered through a short pad of Celite and concentrated to dryness. Recrystallization from EtOAc/hexanes yielded 32.61 g of the title compound as slightly tan crystalline plates, mp 132.5-134° C.: 1H NMR (300 MHz, CD3OD) δ 7.59 (d, J=8.8 Hz, 1H), 7.05 (d, J=2.2 Hz, 1H), 6.92 (dd, J=8.7, 2.4 Hz, 1H), 3.92 (q, J=9.2 Hz, 2H).

1. customremained below 5° C.
2. customslightly exothermic reaction
3. customprecipitated solids
4. filtrationwere collected by filtration
5. customOrganic and aqueous phases of the filtrate were separated
6. extractionthe aqueous layer extracted with CH2Cl2 (3×150 mL)
7. concentrationCombined organic extracts were concentrated to dryness
8. customcollected previously
9. dissolutiondissolved in EtOAc
10. washwashed (H2O, brine)
11. dry with materialdried over Na2SO4
12. filtrationfiltered through a short pad of Celite
13. concentrationconcentrated to dryness
14. customRecrystallization from EtOAc/hexanes