methoxymethyl(trimethyl)silane

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

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 ml of a solution of 20.5 ml of (methoxymethyl)trimethylsilane in dry tetrahydrofuran was cooled under a nitrogen atmosphere. Then 92 ml of a 1.3 M solution of s-butyllithium in cyclohexane was added dropwise thereinto at −78° C. After the completion of the addition, the mixture was stirred at −35° C. for 30 minutes. After adding 10.9 g of 1,3,5-trimethyl-3-azabicyclo[3.3.1]nonan-9-one, the resulting mixture was stirred at room temperature for 2 hours and then poured into a cooled aqueous solution of ammonium chloride. Then it was made alkaline by adding potassium carbonate and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, 9.2 g of the title compound was obtained as a pale-brown oily substance. at −78° C After the completion of the addition the resulting mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was washed with water dried over anhydrous sodium sulfate After distilling off the solvent under reduced pressure

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 ml of a solution of 20.5 ml of (methoxymethyl)trimethylsilane in dry tetrahydrofuran was cooled under a nitrogen atmosphere. Then 92 ml of a 1.3 M solution of s-butyllithium in cyclohexane was added dropwise thereinto at −78° C. After the completion of the addition, the mixture was stirred at −35° C. for 30 minutes. After adding 10.9 g of 1,3,5-trimethyl-3-azabicyclo[3.3.1]nonan-9-one, the resulting mixture was stirred at room temperature for 2 hours and then poured into a cooled aqueous solution of ammonium chloride. Then it was made alkaline by adding potassium carbonate and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, 9.2 g of the title compound was obtained as a pale-brown oily substance. at −78° C After the completion of the addition the resulting mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was washed with water dried over anhydrous sodium sulfate After distilling off the solvent under reduced pressure

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (methoxymethyl)trimethylsilane (694 mg, 5.75 mmol) in tetrahydrofuran (6.8 mL) at −78° C. was added drop-wise sec-butyllithium (1.4 M, 4.45 mL, 6.23 mmol). The solution was warmed to −25° C., held at that temperature for 30 minutes, then cooled to −78° C. To the reaction was added drop-wise 3-(4-chlorophenyl)cyclohexanone (prepared according to the method of G. A. Whitlock et al., Bioorg. Med. Chem. Lett. 2009, 19, 3118-3121) (1.0 g, 4.8 mmol). The reaction was warmed to −25° C. and stirred for 30 minutes, then allowed to slowly warm to room temperature and stir for 48 hours. The reaction was diluted with tetrahydrofuran (10 mL), quenched with saturated aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to provide the crude title compound as a pale yellow oil. Yield: 1.25 g. This material was used directly in the following step. GCMS m/z 236 (M+). cooled to −78° C prepared The reaction was warmed to −25° C. to slowly warm to room temperature stir for 48 hours quenched with saturated aqueous ammonium chloride solution extracted three times with ethyl acetate The combined organic layers were dried over magnesium sulfate concentrated in vacuo

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (methoxymethyl)trimethylsilane (694 mg, 5.75 mmol) in tetrahydrofuran (6.8 mL) at −78° C. was added drop-wise sec-butyllithium (1.4 M, 4.45 mL, 6.23 mmol). The solution was warmed to −25° C., held at that temperature for 30 minutes, then cooled to −78° C. To the reaction was added drop-wise 3-(4-chlorophenyl)cyclohexanone (prepared according to the method of G. A. Whitlock et al., Bioorg. Med. Chem. Lett. 2009, 19, 3118-3121) (1.0 g, 4.8 mmol). The reaction was warmed to −25° C. and stirred for 30 minutes, then allowed to slowly warm to room temperature and stir for 48 hours. The reaction was diluted with tetrahydrofuran (10 mL), quenched with saturated aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to provide the crude title compound as a pale yellow oil. Yield: 1.25 g. This material was used directly in the following step. GCMS m/z 236 (M+). cooled to −78° C prepared The reaction was warmed to −25° C. to slowly warm to room temperature stir for 48 hours quenched with saturated aqueous ammonium chloride solution extracted three times with ethyl acetate The combined organic layers were dried over magnesium sulfate concentrated in vacuo

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

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (methoxymethyl)trimethylsilane (694 mg, 5.75 mmol) in tetrahydrofuran (6.8 mL) at −78° C. was added drop-wise sec-butyllithium (1.4 M, 4.45 mL, 6.23 mmol). The solution was warmed to −25° C., held at that temperature for 30 minutes, then cooled to −78° C. To the reaction was added drop-wise 3-(4-chlorophenyl)cyclohexanone (prepared according to the method of G. A. Whitlock et al., Bioorg. Med. Chem. Lett. 2009, 19, 3118-3121) (1.0 g, 4.8 mmol). The reaction was warmed to −25° C. and stirred for 30 minutes, then allowed to slowly warm to room temperature and stir for 48 hours. The reaction was diluted with tetrahydrofuran (10 mL), quenched with saturated aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to provide the crude title compound as a pale yellow oil. Yield: 1.25 g. This material was used directly in the following step. GCMS m/z 236 (M+). cooled to −78° C prepared The reaction was warmed to −25° C. to slowly warm to room temperature stir for 48 hours quenched with saturated aqueous ammonium chloride solution extracted three times with ethyl acetate The combined organic layers were dried over magnesium sulfate concentrated in vacuo

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 ml of a solution of 20.5 ml of (methoxymethyl)trimethylsilane in dry tetrahydrofuran was cooled under a nitrogen atmosphere. Then 92 ml of a 1.3 M solution of s-butyllithium in cyclohexane was added dropwise thereinto at −78° C. After the completion of the addition, the mixture was stirred at −35° C. for 30 minutes. After adding 10.9 g of 1,3,5-trimethyl-3-azabicyclo[3.3.1]nonan-9-one, the resulting mixture was stirred at room temperature for 2 hours and then poured into a cooled aqueous solution of ammonium chloride. Then it was made alkaline by adding potassium carbonate and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, 9.2 g of the title compound was obtained as a pale-brown oily substance. at −78° C After the completion of the addition the resulting mixture was stirred at room temperature for 2 hours extracted with ethyl acetate The organic layer was washed with water dried over anhydrous sodium sulfate After distilling off the solvent under reduced pressure

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (methoxymethyl)trimethylsilane (694 mg, 5.75 mmol) in tetrahydrofuran (6.8 mL) at −78° C. was added drop-wise sec-butyllithium (1.4 M, 4.45 mL, 6.23 mmol). The solution was warmed to −25° C., held at that temperature for 30 minutes, then cooled to −78° C. To the reaction was added drop-wise 3-(4-chlorophenyl)cyclohexanone (prepared according to the method of G. A. Whitlock et al., Bioorg. Med. Chem. Lett. 2009, 19, 3118-3121) (1.0 g, 4.8 mmol). The reaction was warmed to −25° C. and stirred for 30 minutes, then allowed to slowly warm to room temperature and stir for 48 hours. The reaction was diluted with tetrahydrofuran (10 mL), quenched with saturated aqueous ammonium chloride solution, and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to provide the crude title compound as a pale yellow oil. Yield: 1.25 g. This material was used directly in the following step. GCMS m/z 236 (M+). cooled to −78° C prepared The reaction was warmed to −25° C. to slowly warm to room temperature stir for 48 hours quenched with saturated aqueous ammonium chloride solution extracted three times with ethyl acetate The combined organic layers were dried over magnesium sulfate concentrated in vacuo