ethyl 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:

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:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5 M in hexanes, 1.6 mL, 4 mmol) was added to a solution of diisopropylamine (0.56 mL, 4 mmol) in 5 mL of tetrahydrofuran at −78° C. After 30 minutes, ethyl trimethylsilylacetate (0.73 mL, 4 mmol) was added. After stirring 30 minutes, a solution of the compound of Example 16J (787 mg, 2 mmol) in 8 mL of tetrahydrofuran was added, followed by a rinse of 2 mL of tetrahydrofuran. After 2 hours, the reaction was quenched by the addition of 10 mL of saturated aqueous NH4Cl. After warming to ambient temperature, the mixture was poured into 100 mL of 20% NaCl, then extracted twice with 100 mL of tert-butyl methyl ether. The combined tert-butyl methyl ether extracts were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (300 mL of SiO2, elution with a gradient of 1:1 dichloromethane:hexanes to dichloromethane) to afford 538 mg (58% yield) of a ˜4:1 mixture of isomers favoring the title compound (538 mg, 58%). a rinse of 2 mL of tetrahydrofuran After 2 hours the reaction was quenched by the addition of 10 mL of saturated aqueous NH4Cl the mixture was poured into 100 mL of 20% NaCl extracted twice with 100 mL of tert-butyl methyl ether The combined tert-butyl methyl ether extracts were dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel chromatography ( 300 mL of SiO2, elution with a gradient of 1:1 dichloromethane hexanes to dichloromethane) to afford 538 mg (58% yield) of a ˜4:1 mixture of isomers

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 ethyl trimethlysilylacetate (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 the addition of saturated aqueous NH4Cl; the mixture was warmed to ambient temperature, the 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 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. The title compound was isolated as the slower-eluting material (0.62 g). The reaction was quenched by the addition of saturated aqueous NH4Cl the 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: n-Butyl lithium (4.99 mmol) in hexane was added to N-isopropyl cyclohexylamine (0.69 g, 4.88 mmol, Aldrich Chem Co.) in dry tetrahydrofuran (20 ml) at -78° under nitrogen. After 15 mins, ethyl trimethylsilylacetate (0.78 g, 4.88 mmol, Fluka Chem. Co.) was added. After a further 10 mins, 11-(3',5'-bistrifluoromethylbenzyloxy) undeca-4-ene-3-one (1 g, 2.44 mmol) was added and the temperature was allowed to reach room temperature. After conventional work-up and chromatography on silica, ethyl 11-(3',5'-bistrifluoromethylbenzyloxy)-3-ethyl-undeca-2, 4- dienoate was obtained as a mixture of two isomers. After a further 10 mins to reach room temperature

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

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

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