3-trimethylsilylbenzaldehyde

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:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2 g (87.5 mmol) of sodium in 30 mL of anhydrous EtOH, maintained under a nitrogen atmosphere and cooled to −10° C., is added, dropwise, a mixture of 31.4 mL (87.5 mmol) of ethyl azidoacetate (at 34% in CH2Cl2) and 3.9 g (21.87 mmol) of 3-trimethylsilylbenzaldehyde prepared according to the procedure described in the preceding step, diluted with 3 mL of EtOH. The reaction mixture is stirred at 0° C. for 4 hours. It is then hydrolysed by adding, with vigorous stirring, 100 mL of aqueous NH4Cl solution (30%). The aqueous phase is extracted with 3×50 mL of EtOAc. The combined organic phases are washed with water, dried over Na2SO4 and concentrated under reduced pressure. The crude reaction product is purified by chromatography on a column of silica gel, eluting with an isocratic mixture of heptane and CH2Cl2 (80/20). 1.7 g of the expected ethyl 2-azido-3-(3-trimethylsilylphenyl)propenoate are thus isolated in the form of a yellow oil. is added prepared The aqueous phase is extracted with 3×50 mL of EtOAc The combined organic phases are washed with water dried over Na2SO4 concentrated under reduced pressure The crude reaction product is purified by chromatography on a column of silica gel eluting with an isocratic mixture of heptane and CH2Cl2 (80/20)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5 g (21.89 mmol) of 1-bromo-3-trimethylsilylbenzene prepared according to the protocol described in the preceding step, in 40 mL of anhydrous Et2O, cooled to 0° C. and maintained under a nitrogen atmosphere, are added dropwise, with stirring and over 30 minutes, 16.36 mL (26.18 mmol) of BuLi (1.6M/hexane). Stirring is continued at 0° C. for a further 30 minutes, and the mixture is then maintained at room temperature for 90 minutes. 2.69 mL (34.91 mmol) of DMF, diluted with 17 mL of anhydrous Et2O, are then introduced into the reaction mixture. After stirring for 3 hours at room temperature, the reaction mixture is hydrolysed at 0° C. by successive addition of 10 mL of concentrated HCl solution and 100 mL of water. The product is extracted with 3×50 mL of CH2Cl2. The combined organic phases are washed with 100 mL of water, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude reaction product is purified by flash chromatography on a column of silica gel, eluting with a gradient of from 10 to 20% of CH2Cl2 in heptane to give 1.82 g of the expected 3-trimethylsilylbenzaldehyde in the form of a yellow oil. maintained under a nitrogen atmosphere are added dropwise Stirring is continued at 0° C. for a further 30 minutes the mixture is then maintained at room temperature for 90 minutes are then introduced into the reaction mixture After stirring for 3 hours at room temperature The product is extracted with 3×50 mL of CH2Cl2 The combined organic phases are washed with 100 mL of water dried over Na2SO4 filtered evaporated under reduced pressure The crude reaction product is purified by flash chromatography on a column of silica gel eluting with a gradient of from 10 to 20% of CH2Cl2 in heptane

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 31.4 ml (87.5 mmol) of ethyl azidoacetate (at 34% in CH2Cl2) and 3.9 g (21.87 mmol) of 3-trimethylsilylbenzaldehyde prepared according to the procedure described in stage 3.2, diluted in 3 ml of EtOH, is added dropwise to a solution of 2 g (87.5 mmol) of sodium in 30 ml of anhydrous EtOH, maintained under a nitrogen atmosphere and cooled to −10° C. The reaction mixture is stirred at 0° C. for 4 h. It is subsequently hydrolysed by adding, with vigorous stirring, 100 ml of an aqueous solution of NH4Cl (30%). The aqueous phase is extracted with 3×50 ml of EtOAc. The combined organic phases are washed with water, dried over Na2SO4 and concentrated under reduced pressure. The reaction crude is purified by silica gel column chromatography, elution being carried out with an isocratic mixture of heptane and CH2Cl2 (80/20). 1.7 g of the expected ethyl 2-azido-3-(3-trimethylsilylphenyl)propenoate are thus isolated in the form of a yellow oil. prepared maintained under a nitrogen atmosphere The aqueous phase is extracted with 3×50 ml of EtOAc The combined organic phases are washed with water dried over Na2SO4 concentrated under reduced pressure The reaction crude is purified by silica gel column chromatography, elution being carried out with an isocratic mixture of heptane and CH2Cl2 (80/20)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 16.36 ml (26.18 mmol) of BuLi (1.6N/hexane) are added dropwise, with stirring and over 30 min, to a solution of 5 g (21.89 mmol) of 1-bromo-3-trimethylsilylbenzene prepared according to the protocol described in stage 3.1, in 40 ml of anhydrous Et2O, cooled to 0° C. and maintained under a nitrogen atmosphere. The stirring is continued at 0° C. for a further 30 min, and then maintained at ambient temperature for 90 min. 2.69 ml (34.91 mmol) of DMF, diluted in 17 ml of anhydrous Et2O, are subsequently introduced into the reaction mixture. After stirring for 3 h at ambient temperature, the reaction mixture is hydrolysed at 0° C. by successive additions of 10 ml of a concentrated HCl solution and 100 ml of water. The product is extracted with 3×50 ml of CH2Cl2. The combined organic phases are washed with 100 ml of water, dried over Na2SO4, filtered and evaporated under reduced pressure. The reaction crude is purified by flash chromatography on a silica gel column, elution being carried out with a gradient of 10 to 20% of CH2Cl2 in heptane, to give 1.82 g of expected 3-trimethylsilyl-benzaldehyde in the form of a yellow oil. prepared maintained under a nitrogen atmosphere maintained at ambient temperature for 90 min are subsequently introduced into the reaction mixture The product is extracted with 3×50 ml of CH2Cl2 The combined organic phases are washed with 100 ml of water dried over Na2SO4 filtered evaporated under reduced pressure The reaction crude is purified by flash chromatography on a silica gel column, elution

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

Procedure: To a mixture of 3-trimethylsilylbenzylalcohol (3.60 g, 20 mmol) and pyridium dichromate (11.29 g, 30 mmol) in dichloromethane (60 ml) at 0° C. was added 3 Å molecular sieve powder (16 g) and anhydrous acetic acid (2 ml). Then the reaction was allowed to react 30 min at room temperature, stirred 20 min with celite (10 g), filtered and evaporated under reduced pressure. The residue was treated with diethyl ether (50 ml), filtered through MgSO4 and concentrated. 3-trimethylsilylbenzaldehyde was purified by distillation. to react 30 min at room temperature filtered evaporated under reduced pressure The residue was treated with diethyl ether (50 ml) filtered through MgSO4 concentrated 3-trimethylsilylbenzaldehyde was purified by distillation

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2 g (87.5 mmol) of sodium in 30 mL of anhydrous EtOH, maintained under a nitrogen atmosphere and cooled to −10° C., is added, dropwise, a mixture of 31.4 mL (87.5 mmol) of ethyl azidoacetate (at 34% in CH2Cl2) and 3.9 g (21.87 mmol) of 3-trimethylsilylbenzaldehyde prepared according to the procedure described in the preceding step, diluted with 3 mL of EtOH. The reaction mixture is stirred at 0° C. for 4 hours. It is then hydrolysed by adding, with vigorous stirring, 100 mL of aqueous NH4Cl solution (30%). The aqueous phase is extracted with 3×50 mL of EtOAc. The combined organic phases are washed with water, dried over Na2SO4 and concentrated under reduced pressure. The crude reaction product is purified by chromatography on a column of silica gel, eluting with an isocratic mixture of heptane and CH2Cl2 (80/20). 1.7 g of the expected ethyl 2-azido-3-(3-trimethylsilylphenyl)propenoate are thus isolated in the form of a yellow oil. is added prepared The aqueous phase is extracted with 3×50 mL of EtOAc The combined organic phases are washed with water dried over Na2SO4 concentrated under reduced pressure The crude reaction product is purified by chromatography on a column of silica gel eluting with an isocratic mixture of heptane and CH2Cl2 (80/20)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5 g (21.89 mmol) of 1-bromo-3-trimethylsilylbenzene prepared according to the protocol described in the preceding step, in 40 mL of anhydrous Et2O, cooled to 0° C. and maintained under a nitrogen atmosphere, are added dropwise, with stirring and over 30 minutes, 16.36 mL (26.18 mmol) of BuLi (1.6M/hexane). Stirring is continued at 0° C. for a further 30 minutes, and the mixture is then maintained at room temperature for 90 minutes. 2.69 mL (34.91 mmol) of DMF, diluted with 17 mL of anhydrous Et2O, are then introduced into the reaction mixture. After stirring for 3 hours at room temperature, the reaction mixture is hydrolysed at 0° C. by successive addition of 10 mL of concentrated HCl solution and 100 mL of water. The product is extracted with 3×50 mL of CH2Cl2. The combined organic phases are washed with 100 mL of water, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude reaction product is purified by flash chromatography on a column of silica gel, eluting with a gradient of from 10 to 20% of CH2Cl2 in heptane to give 1.82 g of the expected 3-trimethylsilylbenzaldehyde in the form of a yellow oil. maintained under a nitrogen atmosphere are added dropwise Stirring is continued at 0° C. for a further 30 minutes the mixture is then maintained at room temperature for 90 minutes are then introduced into the reaction mixture After stirring for 3 hours at room temperature The product is extracted with 3×50 mL of CH2Cl2 The combined organic phases are washed with 100 mL of water dried over Na2SO4 filtered evaporated under reduced pressure The crude reaction product is purified by flash chromatography on a column of silica gel eluting with a gradient of from 10 to 20% of CH2Cl2 in heptane