chloro-[2-[chloro(dimethyl)silyl]ethyl]-dimethylsilane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of freshly distilled diisopropylamine (22.9 mL) in dry tetrahydrofuran (175 mL) at −78° C. under N2 is treated with n-butyllithium (1.6M in hexanes, 109 mL) dropwise over 15 minutes, and the resulting mixture is stirred at −78° C. for 45 minutes and is then added over ten minutes via cannula to a solution of 3-fluoroaniline (8.00 mL) in dry tetrahydrofuran (166 mL) at −78° C. under N2. The resulting reaction mixture is stirred at −78° C. for 50 minutes and is then treated with a solution of 1,1,4,4-tetramethyl-1,4-dichlorodisilethylene (18.3 g) in dry tetrahydrofuran (85 mL). The mixture is allowed to slowly warm to ambient temperature over four hours with stirring and is then washed with water (2×200 mL) and saline (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (CDCl3, 400 MHz) 7.12, 6.65, 6.58, 0.86, 0.24δ. The resulting reaction mixture is stirred at −78° C. for 50 minutes to slowly warm to ambient temperature over four hours with stirring is then washed with water (2×200 mL) and saline (100 mL) dried over anhydrous sodium sulfate concentrated under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of freshly distilled diisopropylamine (22.9 mL) in dry tetrahydrofuran (175 mL) at −78° C. under N2 is treated with n-butyllithium (1.6M in hexanes, 109 mL) dropwise over 15 minutes, and the resulting mixture is stirred at −78° C. for 45 minutes and is then added over ten minutes via cannula to a solution of 3-fluoroaniline (8.00 mL) in dry tetrahydrofuran (166 mL) at −78° C. under N2. The resulting reaction mixture is stirred at −78° C. for 50 minutes and is then treated with a solution of 1,1,4,4-tetramethyl-1,4-dichlorodisilethylene (18.3 g) in dry tetrahydrofuran (85 mL). The mixture is allowed to slowly warm to ambient temperature over four hours with stirring and is then washed with water (2×200 mL) and saline (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (CDCl3, 400 MHz) 7.12, 6.65, 6.58, 0.86, 0.24δ. The resulting reaction mixture is stirred at −78° C. for 50 minutes to slowly warm to ambient temperature over four hours with stirring is then washed with water (2×200 mL) and saline (100 mL) dried over anhydrous sodium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-2-chloro-5-fluoro-phenol (104, 2.25 g, 9.98 mmol) in tetrahydrofuran (50 mL), cooled to −78° C. under an atmosphere of nitrogen, was added n-butyllithium (2.50 M in hexane, 4.21 mL) and 1,2-bis-(chloro-dimethyl-silanyl)-ethane (1.08 g, 5.01 mmol). The reaction was stirred at room temperature for 2 hours. The reaction was cooled to −78° C., followed by adding tert-butyllithium (1.70 M in hexane, 12.4 mL). After 30 minutes, N,N-dimethylformamide (0.97 mL, 0.0125 mol) was added to the reaction. After 30 minutes, the reaction was warmed to room temperature for 10 minutes. 5N HCl (20 mL) was added to the reaction. After 30 minutes, the reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (105, 0.50 g, 28.7). 1H NMR consistent with structure. The reaction was cooled to −78° C. After 30 minutes After 30 minutes the reaction was warmed to room temperature for 10 minutes After 30 minutes extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered The filtrate was concentrated purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromo-2-chloro-5-fluoro-phenol (104, 2.25 g, 9.98 mmol) in tetrahydrofuran (50 mL), cooled to −78° C. under an atmosphere of nitrogen, was added n-butyllithium (2.50 M in hexane, 4.21 mL) and 1,2-bis-(chloro-dimethyl-silanyl)-ethane (1.08 g, 5.01 mmol). The reaction was stirred at room temperature for 2 hours. The reaction was cooled to −78° C., followed by adding tert-butyllithium (1.70 M in hexane, 12.4 mL). After 30 minutes, N,N-dimethylformamide (0.97 mL, 0.0125 mol) was added to the reaction. After 30 minutes, the reaction was warmed to room temperature for 10 minutes. 5N HCl (20 mL) was added to the reaction. After 30 minutes, the reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane to give the desired compound (105, 0.50 g, 28.7). 1H NMR consistent with structure. The reaction was cooled to −78° C. After 30 minutes After 30 minutes the reaction was warmed to room temperature for 10 minutes After 30 minutes extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered The filtrate was concentrated purified by silica gel column chromatography eluting with 20% to 100% ethyl acetate in hexane