2,3-difluorobenzoyl chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of t-butyllithium (3.0 mL, 1.2 M in pentane) was added to a cooled (−78° C.) solution of benzyloxy-4-bromobenzene (500 mg, 1.9 mmol) in THF (20 mL). The temperature was raised to −15° C. over a period of 1 h and stirred at −15° C. for an additional 2 h. A slurry of MnCl2.2LiCl2 (1.9 mmol) in THF (13 mL) was added and the mixture was stirred for 30 min allowing the temperature to reach 0° C. 2,3-Difluorobenzoyl chloride was added and the reaction was stirred at r.t. for 1 h. Water (20 mL) was added, stirred for 10 min. The aqueous phase was extracted with dichloromethane (2×20 mL) and the organic phases were combined and washed with brine (20 mL), dried (Na2SO4), filtered and concentrated. Purified by flash chromatography (eluent: 100% heptane →10% ethyl acetate in heptane) to give the title compound 3 (320 mg, 52% yield). 1H-NMR (400 MHz, CDCl3): δ 7.88 (d, J=7.5 Hz, 2H), 7.48-7.15 (m, 8H), 7.08 (d, J=7.5 Hz, 2H), 5.18 (s, 2H). the mixture was stirred for 30 min to reach 0° C the reaction was stirred at r.t. for 1 h stirred for 10 min The aqueous phase was extracted with dichloromethane (2×20 mL) washed with brine (20 mL) dried (Na2SO4) filtered concentrated Purified by flash chromatography (eluent: 100% heptane →10% ethyl acetate in heptane)

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

実験手順: The title compound was prepared in accordance with the general method of Example 199(D), from N-methyl-4-(pyridin-2-yl)but-3-yn-1-amine (50 mg, 0.31 mmol) and 2,3-difluorobenzoyl chloride (72 mg, 0.41 mmol). The crude residue was purified over silicagel chromatography (prepacked 10 g silicagel column, DCM/MeOH: from 100/0 to 98/2 as eluent) to afford 67 mg of 2,3-difluoro-N-methyl-N-(4-(pyridin-2-yl)but-3-ynyl)benzamide as a brown oil (Yield: 71%). The crude residue was purified over silicagel chromatography (prepacked 10 g silicagel column, DCM/MeOH: from 100/0 to 98/2 as eluent)