16.6 g |
Stage #1: 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid With HATU In N,N-dimethyl-formamide at 20℃; for 0.25h;
Stage #2: Cyclopropylamine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; |
0628 Preparation of 2-chloro-N-cyclopropyl-5-(4,4,5,5- tetramethyl- 1 ,3,2-dioxaborolan-2-yl)benzamide
10628] 25.0 g (88.5 mmol) of 2-chloro-5-(4,4,5,5-tetram- ethyl-i ,3,2-dioxaborolan-2-yl)benzoic acid are dissolved in 850 ml of dimethylformamide, and 33.7 g (88.5 mmol) of HATU (1 -[bis(dimethylamino)methylene] -i H-i ,2,3-triazol [4,5-b]pyridinium 3-oxide hexafluorophosphate) are then added. The reaction is stirred at room temperature for 15 minutes. 35.4 ml (199 mmol) of N-ethyl-diisopropylamine and 7.50 ml (106 mmol) of cyclopropylamine are addedto the reaction solution. After 16 h at room temperature, the solvent is distilled offunder reduced pressure. The residue is taken up in water, and the product is subsequently extracted three times with in each case 500 ml of ethyl acetate. The combined organic phases are dried over sodium sulphate and filtered, and the solvent is removed under reduced pressure. The crude product is purified by column chromatography on silica gel. 10629] This gives 16.6 g of 2-chloro-N-cyclopropyl-5-(4, 4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)benzamide as a colourless solid.10630] ‘H-NMR (400 MHz, d5-dimethyl sulphoxide): ö8.50 (d, iH), 7.66 (dd, iH), 7.58 (d, iH), 7.50 (d, iH), 2.77-2.83 (m, iH), 1.29 (s, i2H), 0.66-0.71 (m, 2H), 0.51-0.55 (m, 2H) ppm. |