4-(苯基甲氧基甲基)环己-1-one

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 445C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 mL), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5, 15, 25, 50% ethyl acetate in hexanes step gradient to give the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5, 15, 25, 50% ethyl acetate in hexanes step gradient

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 441C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 mL), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5, 15, 25, 50% ethyl acetate in hexanes step gradient to give the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5, 15, 25, 50% ethyl acetate in hexanes step gradient

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 341C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 ml), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient to provide the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 341C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 ml), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient to provide the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 341C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 ml), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient to provide the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 341C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 ml), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient to provide the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1,4-dioxaspiro[4.5]decan-8-ylmethanol (1.33 g, 7.72 mmol) was dissolved in DMF (14 mL) and then cooled to 0° C. To the solution was added NaH (0.402 g, 10.04 mmol) in portions and the mixture agitated at 10° C. for 1 h and then benzyl bromide (1.194 mL, 10.04 mmol) was added and the mixture agitated over 72 h. The reaction mixture was quenched with water and extracted with ether and the combined organic extracts dried (MgSO4), filtered and concentrated in vacuo and the crude product 8-((benzyloxy)methyl)-1,4-dioxaspiro[4.5]decane dissolved in acetonitrile (35 mL) and water (25 mL) and treated with 3N HCl (13 mL) and agitated at room temperature for 20 min upon which LCMS indicated desired product. The reaction mixture was quenched with 40 mmol aqueous NaOH and then extracted with EtOAc (200 mL) and the organic layer was washed with water and dried (MgSO4), filtered and concentrated in vacuo and the residue purified by flash chromatography (0-50% EtOAc/heptane) to afford 1.23 g of the desired product as a colorless syrup (73%). LCMS (m/z): 329.2 (MH+), 1.33 min. the mixture agitated over 72 h The reaction mixture was quenched with water extracted with ether the combined organic extracts dried (MgSO4) filtered concentrated in vacuo the crude product 8-((benzyloxy)methyl)-1,4-dioxaspiro[4.5]decane dissolved in acetonitrile (35 mL) water (25 mL) and treated with 3N HCl (13 mL) agitated at room temperature for 20 min upon which LCMS extracted with EtOAc (200 mL) the organic layer was washed with water dried (MgSO4) filtered concentrated in vacuo the residue purified by flash chromatography (0-50% EtOAc/heptane)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyltriphenylphosphonium bromide (12.27 g) and anhydrous tetrahydrofuran (60.0 mL) was cooled to −78° C. A suspension of potassium t-butoxide (4.37 g) in tetrahydrofuran (60.0 mL) was added dropwise. The mixture was stirred at 0° C. for 1 hour and then for 1 hour as the reaction warmed to ambient temperature. The reaction mixture was cooled to −40° C. and a solution of EXAMPLE 341D (5 g,) in tetrahydrofuran (35 mL) was added dropwise. After stirring 18 hours at ambient temperature, the reaction was quenched by the careful addition of 33% brine (150 mL) and diluted with ether (150 mL). The layers were separated and the aqueous layer was extracted with ether (2×75 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel and eluted with a 0, 10, 15, 25% ethyl acetate in hexane step gradient to provide the title compound. was added dropwise for 1 hour as the reaction warmed to ambient temperature The reaction mixture was cooled to −40° C. After stirring 18 hours at ambient temperature the reaction was quenched by the careful addition of 33% brine (150 mL) diluted with ether (150 mL) The layers were separated the aqueous layer was extracted with ether (2×75 mL) The combined organics were dried over sodium sulfate filtered concentrated The residue was purified on silica gel eluted with a 0, 10, 15, 25% ethyl acetate in hexane step gradient

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of EXAMPLE 341D (5 g), zinc iodide (0.183 g) and anhydrous ether (50 mL) was cooled in an ice bath and trimethylsilanecarbonitrile (3.45 mL) was added dropwise. The reaction was allowed to warm to ambient temperature with stirring continued 45 minutes. The reaction mixture was added via a syringe to a suspension of lithium aluminum hydride (2.78 g) in ether (75 mL) dropwise and the reaction mixture was then heated at reflux for 2 hours. The reaction was cooled in an ice bath and quenched very slowly by careful addition of water (2.8 mL), keeping the temperature below 5° C. Ether (100 mL) was added, followed by 4N aqueous sodium hydroxide (2.8 mL) and water (8.4 mL). The mixture was further diluted with ether (150 mL) and anhydrous sodium sulfate (70 g) was added. The resulting suspension was stirred for 18 hours and filtered. The solids were washed with ether (4×150 mL). The combined organics were dried with Na2SO4, filtered, and concentrated to provide the title compound. the reaction mixture was then heated at reflux for 2 hours The reaction was cooled in an ice bath quenched very slowly by careful addition of water (2.8 mL) the temperature below 5° C Ether (100 mL) was added The mixture was further diluted with ether (150 mL) and anhydrous sodium sulfate (70 g) was added The resulting suspension was stirred for 18 hours filtered The solids were washed with ether (4×150 mL) The combined organics were dried with Na2SO4 filtered concentrated

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of EXAMPLE 341C (43.02 g) in dioxane (500 mL) was added water (125 mL) and 2M hydrochloric acid (90 mL). The mixture was heated at 85° C. for 18 hours. Upon cooling, the reaction mixture was diluted with brine (1500 ml), saturated sodium bicarbonate solution (300 mL) and ether (1000 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient to provide the title compound. Upon cooling The organic layer was dried over sodium sulfate filtered concentrated The crude product was purified on silica gel eluting with a 5-50% ethyl acetate in hexanes step gradient