methyl 2-trimethylsilylacetate

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

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

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

Procedure: A solution of diisopropylamine (1.2 mL, 9.4 mmol) in 10 mL of tetrahydrofuran was cooled to −78° C.; n-butyllithium (2.5 M in hexanes, 3.6 mL) was added, followed after 5 minutes by methyl trimethylsilylacetate (1.7 mL). The resultant solution was stirred at −78° C. for 30 minutes, and then a solution of the compound of Example 13E (2.0 g, 4 mmol) in 10 mL of tetrahydrofuran was added over 5 minutes. Stirring was continued for 4 hours. The reaction was quenched by addition of saturated aqueous NH4Cl; the mixture was warmed to ambient temperature, and partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl and brine, and dried over Na2SO4. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 5% to 10% ethyl acetate in hexanes. The product (1.9 g) was dissolved in 17 mL of ethanol; 1.3 mL of concentrated HCl was added, and the resultant solution was stirred overnight at ambient temperature. The solvents were removed in vacuo, the residue was taken up in saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was concentrated in vacuo and purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 2% to 3% dichloromethane in acetonitrile to afford the titled compound (0.76 g). The reaction was quenched by addition of saturated aqueous NH4Cl partitioned between ethyl acetate and water The organic phase was washed with 1 N aqueous HCl and brine dried over Na2SO4 The solvents were removed in vacuo the residue was purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 5% to 10% ethyl acetate in hexanes The product (1.9 g) was dissolved in 17 mL of ethanol 1.3 mL of concentrated HCl was added the resultant solution was stirred overnight at ambient temperature The solvents were removed in vacuo extracted with ethyl acetate The organic phase was concentrated in vacuo purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 2% to 3% dichloromethane in acetonitrile

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

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

Procedure: A solution of diisopropylamine (1.2 mL, 9.4 mmol) in 10 mL of tetrahydrofuran was cooled to −78° C.; n-butyllithium (2.5 M in hexanes, 3.6 mL) was added, followed after 5 minutes by methyl trimethylsilylacetate (1.7 mL). The resultant solution was stirred at −78° C. for 30 minutes, and then a solution of the compound of Example 13E (2.0 g, 4 mmol) in 10 mL of tetrahydrofuran was added over 5 minutes. Stirring was continued for 4 hours. The reaction was quenched by addition of saturated aqueous NH4Cl; the mixture was warmed to ambient temperature, and partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl and brine, and dried over Na2SO4. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 5% to 10% ethyl acetate in hexanes. The product (1.9 g) was dissolved in 17 mL of ethanol; 1.3 mL of concentrated HCl was added, and the resultant solution was stirred overnight at ambient temperature. The solvents were removed in vacuo, the residue was taken up in saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was concentrated in vacuo and purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 2% to 3% dichloromethane in acetonitrile to afford the titled compound (0.76 g). The reaction was quenched by addition of saturated aqueous NH4Cl partitioned between ethyl acetate and water The organic phase was washed with 1 N aqueous HCl and brine dried over Na2SO4 The solvents were removed in vacuo the residue was purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 5% to 10% ethyl acetate in hexanes The product (1.9 g) was dissolved in 17 mL of ethanol 1.3 mL of concentrated HCl was added the resultant solution was stirred overnight at ambient temperature The solvents were removed in vacuo extracted with ethyl acetate The organic phase was concentrated in vacuo purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 2% to 3% dichloromethane in acetonitrile

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

Procedure: A solution of diisopropylamine (1.2 mL, 9.4 mmol) in 10 mL of tetrahydrofuran was cooled to −78° C.; n-butyllithium (2.5 M in hexanes, 3.6 mL) was added, followed after 5 minutes by methyl trimethylsilylacetate (1.7 mL). The resultant solution was stirred at −78° C. for 30 minutes, and then a solution of the compound of Example 13E (2.0 g, 4 mmol) in 10 mL of tetrahydrofuran was added over 5 minutes. Stirring was continued for 4 hours. The reaction was quenched by addition of saturated aqueous NH4Cl; the mixture was warmed to ambient temperature, and partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl and brine, and dried over Na2SO4. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 5% to 10% ethyl acetate in hexanes. The product (1.9 g) was dissolved in 17 mL of ethanol; 1.3 mL of concentrated HCl was added, and the resultant solution was stirred overnight at ambient temperature. The solvents were removed in vacuo, the residue was taken up in saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was concentrated in vacuo and purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 2% to 3% dichloromethane in acetonitrile to afford the titled compound (0.76 g). The reaction was quenched by addition of saturated aqueous NH4Cl partitioned between ethyl acetate and water The organic phase was washed with 1 N aqueous HCl and brine dried over Na2SO4 The solvents were removed in vacuo the residue was purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 5% to 10% ethyl acetate in hexanes The product (1.9 g) was dissolved in 17 mL of ethanol 1.3 mL of concentrated HCl was added the resultant solution was stirred overnight at ambient temperature The solvents were removed in vacuo extracted with ethyl acetate The organic phase was concentrated in vacuo purified by chromatography on an Analogix Intelliflash 280™ eluting with a gradient of 2% to 3% dichloromethane in acetonitrile

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

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

Procedure: Lithium bis(trimethylsilyl)amide (3.46 mmol, 1M in THF) was added dropwise to a solution of methyl trimethylsilylacetate (3.46 mmol) in THF (5 mL) at −78° C. After 20 minutes at −78° C., a solution of 10.2 (2.16 mmol) in THF (9 mL) was added dropwise and the reaction was maintained at −78° C. for 1.5 hours. The reaction was quenched with water and extracted with EtOAc. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed (silica gel, 1:1 EtOAc/hexane) to afford compound 10.3. MS ESI (pos.) m/e 330.1 (M+1). The reaction was quenched with water extracted with EtOAc The organic phase was washed with brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was chromatographed (silica gel, 1:1 EtOAc/hexane)

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

Procedure: Lithium bis(trimethylsilyl)amide (3.46 mmol, 1M in THF) was added dropwise to a solution of methyl trimethylsilylacetate (3.46 mmol) in THF (5 mL) at −78° C. After 20 minutes at −78° C., a solution of 10.2 (2.16 mmol) in THF (9 mL) was added dropwise and the reaction was maintained at −78° C. for 1.5 hours. The reaction was quenched with water and extracted with EtOAc. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed (silica gel, 1:1 EtOAc/hexane) to afford compound 10.3. MS ESI (pos.) m/e 330.1 (M+1). The reaction was quenched with water extracted with EtOAc The organic phase was washed with brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was chromatographed (silica gel, 1:1 EtOAc/hexane)

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

Procedure: Lithium bis(trimethylsilyl)amide (3.46 mmol, 1M in THF) was added dropwise to a solution of methyl trimethylsilylacetate (3.46 mmol) in THF (5 mL) at −78° C. After 20 minutes at −78° C., a solution of 10.2 (2.16 mmol) in THF (9 mL) was added dropwise and the reaction was maintained at −78° C. for 1.5 hours. The reaction was quenched with water and extracted with EtOAc. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed (silica gel, 1:1 EtOAc/hexane) to afford compound 10.3. MS ESI (pos.) m/e 330.1 (M+1). The reaction was quenched with water extracted with EtOAc The organic phase was washed with brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was chromatographed (silica gel, 1:1 EtOAc/hexane)

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

Procedure: At −78° C., lithium bis(trimethylsilyl)amide (1.0 M in THF) (3.6 mL, 3.6 mmol) was added slowly to a solution of methyl 2-(trimethylsilyl)acetate (0.59 mL, 3.6 mmol) in THF (20 mL). The mixture was maintained at −78° C. for 7 minutes and then 6-(benzyloxy)-2,2-dimethyl-2,3-dihydroinden-1-one (8.3) (0.535 g, 2.0 mmol) was added in one portion. The resulting mixture was stirred at −78° C. and allowed to warm to room temperature overnight. The reaction mixture was then diluted with EtOAc (200 mL), washed with water and brine, and dried over anhydrous sodium sulfate. After removing solvent, the residue was purified by chromatography (silica gel, 1:5 EtOAc/hexane) to give product 8.4 in 45% yield. to warm to room temperature overnight washed with water and brine dried over anhydrous sodium sulfate After removing solvent the residue was purified by chromatography (silica gel, 1:5 EtOAc/hexane)

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

Procedure: At −78° C., lithium bis(trimethylsilyl)amide, (1.0 M in hexanes) (5 mL, 28 mmol) was added slowly to a solution of methyl 2-(trimethylsilyl)acetate (4 g, 28 mmol) in THF (30 mL). The reaction was maintained at −78° C. for 16 minutes and then 7-nitro-1-tetralone 6.1 (available from Astratech) (3 g, 16 mmol) was added in one portion, and the resulting mixture was stirred at −78° C. and allowed to warm to room temperature for 20 hours. The resulting mixture was poured into water (30 mL) and then extracted with EtOAc (300 mL). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After removing solvent, the residue was purified by chromatography (silica gel, 1:4 EtOAc/hexane) to give 6.2 in 83% yield. to warm to room temperature for 20 hours extracted with EtOAc (300 mL) The combined organic layers were washed with brine dried over anhydrous sodium sulfate After removing solvent the residue was purified by chromatography (silica gel, 1:4 EtOAc/hexane) to give 6.2 in 83% yield