2-(difluoromethyl)-4-fluorobenzaldehyde

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture containing 2-(difluoromethyl)-4-fluorobenzaldehyde (47; 3.50 g, 20.1 mmol), morpholine (48; 1.9 g, 22.1 mmol) and K2CO3 (5.5 g, 40.2 mmol) in 50 mL of DMSO was stirred at 100° C. for 4 h. The resulting reaction mixture was cooled to room temperature and diluted with water (200 mL). The precipitated solids were collected by filtration and dried to afford 2-(difluoromethyl)-4-morpholinobenzaldehyde 49 (2.5 g, 52%). The resulting reaction mixture was cooled to room temperature The precipitated solids were collected by filtration dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same general procedure outlined above for the preparation of benzimidazole was used employing 2-(difluoromethyl)-4-fluorobenzaldehyde 45 and 2,3-diaminobenzoic acid 1 as the starting materials to afford 2-(2-(difluoromethyl)-4-fluorophenyl)-1H-benzo[d]imidazole-4-carboxylic acid 46. MS (ESI) calcd for C15H9F3N2O2: 306.6; found: 307 [M+H].

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropyl magnesium bromide (30 mL, 1M in THF, 30 mmol) was added dropwise to an ice-cooled solution of 1-bromo-2-(difluoromethyl)-4-fluorobenzene (44; 6 g, 26.7 mmol) in THF (100 mL). The reaction mixture was then allowed to warm to room temperature and stirred for 3 hr. Dimethylformamide (3.5 ml, 45.2 mmol) was added and the reaction stirred for 3 hr. Water was added and the mixture was extracted with ethyl acetate. The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography to afford 2-(difluoromethyl)-4-fluorobenzaldehyde 45 (3.2 g, 68.5%) the reaction stirred for 3 hr the mixture was extracted with ethyl acetate The combined organic layers were dried (Na2SO4) concentrated under reduced pressure The resulting residue was purified by chromatography