trimethyl(2-trimethylsilyloxyethoxy)silane

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: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

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

Procedure: To a solution of trimethylsilyltrifluoromethanesulfonate (0.034 mL) in dry dichloromethane (5 mL) was added 1,2-bis(trimethylsiloxy)ethane (4.55 mL) followed by methyl 3-oxocyclohexanecarboxylate (2.9 g). The reaction mixture was stirred for 3 hours at −78° C. The reaction mixture was quenched with dry pyridine (0.5 mL), poured into saturated aqueous NaHCO3, and extracted with ether. The ether layer was dried over Na2CO3/Na2SO4. The reaction mixture was concentrated and purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes to provide the title compound. The reaction mixture was quenched with dry pyridine (0.5 mL) poured into saturated aqueous NaHCO3 extracted with ether The ether layer was dried over Na2CO3/Na2SO4 The reaction mixture was concentrated purified by flash chromatography on silica with 5 to 30% ethyl acetate in hexanes

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

Procedure: In a round bottom flask equipped with a magnetic stirbar is placed 1,2-bis(trimethylsilyloxy)ethane (1.3 eq.) in CH2Cl2 containing trimethysilyltrifluoromethanesulfonate at -78° C. To this is added, within 20 minutes, a solution of 1 (1 eq) in CH2Cl2. The reaction is stirred for 1 hour at -78° C. and then slowly warmed to 25° C. for 1 hour. The reaction is quenched at 0° C. with water, extracted with CH2Cl2 (3 times), dried (MgSO4), and concentrated in vacuo to give crude 2. To a well stirred solution of crude 2 (1 eq) in methanol at 0° C. is added a suspension of sodium methoxide (1.2 eq) in MeOH. The reaction is stirred at 0° C. for 1 hour and then warmed to 25° C. for 1 hour. The reaction is neutralized with acidic ion exchange resin which is washed thoroughly with MeOH (5×). The filtrate is concentrated in vacuo to give a syrup which is subjected to flash chromatography on silica gel eluting with 4:1 hexane:ethyl acetate and 2% MeOH in CH2Cl2 to give 3. In a round bottom flask equipped with a magnetic stirbar To this is added, within 20 minutes slowly warmed to 25° C. for 1 hour The reaction is quenched at 0° C. with water extracted with CH2Cl2 (3 times) dried (MgSO4) concentrated in vacuo to give crude 2 The reaction is stirred at 0° C. for 1 hour warmed to 25° C. for 1 hour is washed thoroughly with MeOH (5×) The filtrate is concentrated in vacuo to give a syrup which

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

Procedure: In a round bottom flask equipped with a magnetic stirbar is placed 1,2-bis(trimethylsilyloxy)ethane (1.3 eq.) in CH2Cl2 containing trimethysilyltrifluoromethanesulfonate at -78° C. To this is added, within 20 minutes, a solution of 1 (1 eq) in CH2Cl2. The reaction is stirred for 1 hour at -78° C. and then slowly warmed to 25° C. for 1 hour. The reaction is quenched at 0° C. with water, extracted with CH2Cl2 (3 times), dried (MgSO4), and concentrated in vacuo to give crude 2. To a well stirred solution of crude 2 (1 eq) in methanol at 0° C. is added a suspension of sodium methoxide (1.2 eq) in MeOH. The reaction is stirred at 0° C. for 1 hour and then warmed to 25° C. for 1 hour. The reaction is neutralized with acidic ion exchange resin which is washed thoroughly with MeOH (5×). The filtrate is concentrated in vacuo to give a syrup which is subjected to flash chromatography on silica gel eluting with 4:1 hexane:ethyl acetate and 2% MeOH in CH2Cl2 to give 3. In a round bottom flask equipped with a magnetic stirbar To this is added, within 20 minutes slowly warmed to 25° C. for 1 hour The reaction is quenched at 0° C. with water extracted with CH2Cl2 (3 times) dried (MgSO4) concentrated in vacuo to give crude 2 The reaction is stirred at 0° C. for 1 hour warmed to 25° C. for 1 hour is washed thoroughly with MeOH (5×) The filtrate is concentrated in vacuo to give a syrup which

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (3R*,4R*)-N,N-diethyl-6-diphenylmethyl-5-oxo-1-azabicyclo[2.2.2]octane-3-carboxamide (10 g, 26 mmol), 1,2-bis(trimethylsiloxy)ethane (6 g, 29 mmol), trimethylsilyl chloride (20 ml) and ethylene glycol (50 ml) was heated at 100° C. for 3 hours. After by-products were removed by distillation (93° C./atmosphere pressure), the mixture was poured into cold aqueous sodium bicarbonate (NaHCO3) (250 ml) and extracted with methylene chloride (CH2Cl2) (100 ml) three times. The combined extracts were dried over sodium sulfate (Na2SO4) and concentrated. The clude was purified by recrystallization from ethyl acetate (EtOAc)/hexane to give 21 (1:2 mixture at 6-position; 23 mmol, 88%). After by-products were removed by distillation (93° C./atmosphere pressure) the mixture was poured into cold aqueous sodium bicarbonate (NaHCO3) (250 ml) extracted with methylene chloride (CH2Cl2) (100 ml) three times The combined extracts were dried over sodium sulfate (Na2SO4) concentrated The clude was purified by recrystallization from ethyl acetate (EtOAc)/hexane

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

Procedure: In a manner similar to that described in Tsunoda T., et al., Tet. Lett., 1980, 21(14), 1357-1358, Hwa et al., J. Org. Chem., 1987, 52(2), 188-191. A solution of 3β-acetoxy-17β-t-butyldimethylsilyloxy-androst-5-en-7-one (40.000 g, 86.821 mmol) from Example 16B or otherwise obtained and 1,2-bis(trimethylsiloxy)ethane (23.00 mL, 93.81 mmole) in CH2Cl2 (300 mL) is prepared at −78° C. Trimethylsilyl trifluoromethanesulfonate (0.20 mL, 1.035 mmol) is added under an inert atmosphere, the reaction is stirred for three hours, pyridine (2.00 mL, 24.73 mmol) is added and the stirred mixture is allowed to warm to room temperature. The organic solution is poured into saturated aqueous NaHCO3 (300 mL) and the resultant biphasic solution is extracted with EtOAc (3×300 mL). The combined organic extracts are washed with brine (200 mL), dried over MgSO4, filtered and evaporated to dryness. The residue is purified by flash chromatography (1:4 EtOAc/hexane) to give 7,7-ethylenedioxy-17β-t-butyldimethylsilylyoxy-androst-5-en-3-ol 3-acetate. the resultant biphasic solution is extracted with EtOAc (3×300 mL) The combined organic extracts are washed with brine (200 mL) dried over MgSO4 filtered evaporated to dryness The residue is purified by flash chromatography (1:4 EtOAc/hexane)