2-methyl-2-trimethylsilyloxypropanenitrile

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

実験手順: To magnesium turnings (888 mg) in diethyl ether (60 mL) was added 1-bromo-4-[(cyclopropylmethyl)thio]benzene (8.4 g). The mixture was heated at reflux for 16 hrs, and then cooled to ambient temperature. A solution of 2-methyl-2-[(trimethylsilyl)oxy]propanenitrile (4.35 g) in diethyl ether (30 mL) was then added and this solution was stirred at ambient temperature for 7 h. Sodium borohydride (1.33 g) in methanol (30 mL) was then slowly added and the solution aged for 2 h Water (25 mL) was added followed by 1N hydrochloric acid (100 mL) and the mixture stirred for 1 h. The organic layer was extracted with a further portion of 1N hydrochloric acid (100 mL) and the acid extracts combined. These were then made basic with 4N sodium hydroxide solution and extracted with dichloromethane (2×100 mL). The organic extracts were dried (MgSO4) and concentrated to give the title compound as a yellow solid (3.7 g). 1H NMR (360 MHz, CDCl3): δ 7.22-7.34 (4H, m), 3.77 (1H, s), 2.85 (2H, d, J=7.0 Hz), 1.21 (3H, s), 1.09-1.03 (1H, m), 1.03 (3H, s), 0.57 (2H, q, J=5.1 Hz), 0.24 (2H, q, J=5.1 Hz); m/z 307 (M-16[NH2])+. The mixture was heated at reflux for 16 hrs the solution aged for 2 h the mixture stirred for 1 h The organic layer was extracted with a further portion of 1N hydrochloric acid (100 mL) extracted with dichloromethane (2×100 mL) The organic extracts were dried (MgSO4) concentrated

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

実験手順: In a dry 250 ml three necked flask was placed magnesium turnings (2.46 g, 101.2 mmol), 5 ml dry THF and two drops of 1,2-dibromoethane, stirred under N2 at room temperature. Subsequently 1,4-dibromobenzene (19.8 g, 84 mmol) in 15 ml dry THF was added dropwise over 30 min. An ice water bath was occasionally used to moderate the reaction. After addition was complete the reaction was stirred for 2 hrs to complete conversion of bromobenzene. A solution of 2-methyl-2-trimethylsilanyloxy-propionitrile (13.25 g, 85 mmol) in 15 ml dry THF was added dropwise to the Grignard reagent and the mixture was stirred for 20 hrs. By this time a large quantity of white precipitate was formed. The intermediate produced was hydrolyzed by cautious addition of 80 ml 6N HCl with ice cooling and vigorous stirring as the solution warmed to room temperature and then kept stirring at this temperature for 4 hrs. Solid sodium bicarbonate was added cautiously to neutralize the excess acid and the solid in the mixture was removed by vacuum filtration through a pad of Celite and the Celite pad was washed three more times with ethyl acetate. The filtrate was extracted three times with ethyl acetate, dried over anhydrous MgSO4. The solvent was removed by rotary evaporation and the product obtained as liquid, which was suitable for direct use in the next step. For further characterization one gram of the crude product was purified by silica gel column chromatography using EtOAc/hexane 1/4 as eluent. Calculated yield: (77%). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J=8.4 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 4.01 (s, 1H), 1.51 (s, 6H). 13C NMR (100 MHz, (100 MHz, CDCl3) δ 203.21, 134.46, 132.63, 131.28, 127.68, 76.66, 28.11. An ice water bath was occasionally used the reaction After addition was stirred for 2 hrs the mixture was stirred for 20 hrs By this time a large quantity of white precipitate was formed The intermediate produced vigorous stirring as the solution warmed to room temperature kept stirring at this temperature for 4 hrs the solid in the mixture was removed by vacuum filtration through a pad of Celite the Celite pad was washed three more times with ethyl acetate The filtrate was extracted three times with ethyl acetate dried over anhydrous MgSO4 The solvent was removed by rotary evaporation the product obtained as liquid, which For further characterization one gram of the crude product was purified by silica gel column chromatography