86% |
With potassium acetate In dichloromethane; dimethyl sulfoxide at 90℃; for 7.5h; |
8.P'
A 25 mL DMSO mixture of 4-bromo-N-tert-butyl-benzenesulfonamide (CAS 93281-65-3) (2000 mg, 6.84 mmol), bis (pinacolato)diboron mg, 8.21 mmol), [1,1 bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with CH2C12 (1:1) (175 mg, 240 mmol), and KOAc (2020 mg, 20.5 mmol) is stirred under N2 at 90° C for 7.5 hours. Reaction mixture is allowed to cool, is diluted with H20 and is extracted with CH2C12. The CH2C12 extract is washed with H20 and brine, dried (Na2S04) and evaporated. The crude product is purified by silica-gel column chromatography (gradient: 100% CH2C12 to 5% EtOAc/ CH2C12) give the intermediate N-tert-butyl-4-(4,4,5,5- tetramethyl- [1,3,2]dioxaborolan-2-yl)-benzenesulfonamide (2000 mg, 86% yield). (MS (ES-) 256 (boronic acid). |
86% |
Stage #1: 4-bromo-N-(tert-butyl)benzenesulfonamide; bis(pinacol)diborane With potassium acetate In dimethyl sulfoxide at 20 - 90℃; for 7.5h;
Stage #2: With water In dimethyl sulfoxide |
20
Place t-butylamine (4.32 mL, 41.1 mmol), triethylamine (8.15 mL, 58.7 mmol) and dichloromethane (75 mL) in a 3-neck round bottom flask. Cool this stirring solution to 0°C and add a solution of 4-bromobenzenesulfonyl chloride (10.0 g, 39. 1 mmol) in dichloromethane (50 mL). Add additional dichloromethane (25 mL) and stir the reaction overnight, allowing it to warm to ambient temperature. Evaporate the reaction in vacuo. Suspend the resulting white solid in ethyl acetate and filter it. Concentrate the filtrate in vacuo and purify the resulting residue by flash chromatography (silica gel ; 50%-80% gradient CH2C12 in hexanes) to provide 9.85 g of 4-bromo-N-tert-butyl- benzenesulfonamide (86%). Place 4-bromo-N-tert-butyl-benzenesulfonamide (2.00 g, 6. 84 mmol), bis (pinacolato) diboron (2.09 g, 8.21 mmol), PdC12 (dppf) 2'CH2CI2 (175 mg, 0.24 mmol), potassium acetate (2.02 g, 20.5 mmol) and anhydrous dimethyl sulfoxide (25 mL) in a round bottom flask. Put the reaction in an oil bath and stir it at 90°C for 7. 5 hours. Cool the purple colored reaction to ambient temperature, quench with ample water and extract the resulting aqueous mixture into dichloromethane. Wash the combined extracts with water and brine; then dry (sodium sulfate) and evaporate them in vacuo. Purify the resulting dark solid on a flash column (silica gel; 0%-5% gradient of EtOAc in CH2C12) to provide 2.00 g of the title compound (86%). |
86% |
With potassium acetate In dimethyl sulfoxide at 90℃; for 7.5h; Inert atmosphere; |
8
Intermediate Preparation 8N-tert-Butyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzenesulfonamide Procedure P': A 25 mL DMSO mixture of 4-bromo-N-tert-butyl-benzenesulfonamide (CAS 93281-65-3) (2000 mg, 6.84 mmol), bis(pinacolato)diboron (2090 mg, 8.21 mmol), [1,1 bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with CH2Cl2 (1:1) (175 mg, 240 mmol), and KOAc (2020 mg, 20.5 mmol) is stirred under N2 at 90° C. for 7.5 hours. Reaction mixture is allowed to cool, is diluted with H2O and is extracted with CH2Cl2. The CH2Cl2 extract is washed with H2O and brine, dried (Na2SO4) and evaporated. The crude product is purified by silica-gel column chromatography (gradient: 100% CH2Cl2 to 5% EtOAc/CH2Cl2) give the intermediate N-tert-butyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzenesulfonamide (2000 mg, 86% yield). (MS (ES-) 256 (boronic acid). |