5-(2-methoxyphenyl)cyclohexane-1,3-dione

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: The title compound was prepared from 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (1.0 g, 4.58 mmol), example 1/a, and sodium acetate (376 mg, 4.58 mmol), following the procedure describing the synthesis of 2-acetyl-5-(4-fluoro-phenyl)-cyclohexane-1,3-dione (example 3/a stage 1).

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

Procedure: The title compound was prepared from 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (386 mg, 1.77 mmol), example 1/a, and N,N-dimethylformamide dimethylacetal (2 ml), following the procedure described for 5-(4-chloro-phenyl)-2-dimethylaminomethylene-cyclohexane-1,3-dione (example 2/a stage 1) except that the reaction was run at 100° C. for 2 h, after which the solvent was removed by evaporation under reduced pressure to produce the title compound as a brown oil. The title compound was used without further purification in the next step. after which the solvent was removed by evaporation under reduced pressure

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

Procedure: The title compound was prepared from 4-(2-bromo-4-fluoro-phenyl)-but-3-en-2-one (34 g, 142 mmol), stage 1, following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).

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

Procedure: The title compound was prepared from 4-(2-bromo-phenyl)-but-3-en-2-one (1.2 g, 4.44 mmol), stage 1, following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).

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

Procedure: The title compound was prepared from 4-(3-fluoro-phenyl)-but-3-en-2-one stage 1 (940 mg, 5.73 mmol), following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).

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

Procedure: The title compound was prepared from 4-p-tolyl-but-3-en-2-one stage 1 (4.8 g, 30.0 mmol), following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).

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

Procedure: The title compound was prepared from 4-(2-fluoro-phenyl)-but-3-en-2-one (7.3 g, 44.5 mmol), stage 1, following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).

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

Procedure: To a stirred solution of NaOEt (21% in EtOH) (9.8 ml, 26.5 mmol) under nitrogen was added diethylmalonate (3.7 ml, 24.3 mmol). The reaction mixture was stirred at ambient temperature for 20 min. 4-(2-methoxy-phenyl)-but-3-en-2-one (3.89 g, 22.1 mmol), Stage 1, was dissolved in ethanol (20 ml) and added to the reaction mixture, which was stirred at reflux and monitored by LC-MS until 4-(2-methoxy-phenyl)-but-3-en-2-one was consumed. The reaction mixture was cooled to ambient temperature. An aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which was heated at 80° C. for 1.5 h. Excess ethanol was removed by evaporation and the aqueous phase was washed with toluene (20 ml). The aqueous phase was acidified with conc. HCl (5 ml) and the reaction mixture was refluxed for 1 h and left to cool to ambient temperature. The compound was extracted with ethyl acetate (2×30 ml), dried with MgSO4 and filtered. The solvent was removed under reduced pressure. The title compound was purified by column chromatography eluting with ethyl acetate/heptane (1/1) to give a beige solid. added to the reaction mixture, which was stirred at reflux was consumed The reaction mixture was cooled to ambient temperature An aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which was heated at 80° C. for 1.5 h Excess ethanol was removed by evaporation the aqueous phase was washed with toluene (20 ml) the reaction mixture was refluxed for 1 h left to cool to ambient temperature The compound was extracted with ethyl acetate (2×30 ml) dried with MgSO4 filtered The solvent was removed under reduced pressure The title compound was purified by column chromatography eluting with ethyl acetate/heptane (1/1) to give a beige solid

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

Procedure: To a mixture of 5-(2-methoxyphenyl)-1,3-cyclohexanedione (1.0 g), 1-amino-2-butyne hydrochloride (0.5 g), molecular sieves 4A (2 g) and tetrahydrofuran (20 ml) was added triethylamine (0.48 g). The mixture was stirred at room temperature for 1 hour, refluxed for 12 hours and cooled, and insoluble materials were filtered off. Under reduced pressure, the solvent was evaporated, and the residue was stirred for 4 hours at 220° C. and cooled, to which was added ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water and saturated brine, dried with magnesium sulfate and concentrated under reduced pressure, and the residue was purified with silica gel column chromatography (EtOAc/hexane) to give oil of 7-(2-methoxyphenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.4 g). refluxed for 12 hours cooled insoluble materials were filtered off Under reduced pressure, the solvent was evaporated the residue was stirred for 4 hours at 220° C. cooled, to which was added ethyl acetate and sodium hydrogen carbonate solution The organic layer was washed with water and saturated brine dried with magnesium sulfate concentrated under reduced pressure the residue was purified with silica gel column chromatography (EtOAc/hexane)

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

Procedure: To a solution of 5-(2-methoxyphenyl)cyclohexane-1,3-dione (mp144-145° C.; 1.09 g) in DMF (15 ml) was added 60% sodium hydride (0.22 g), and the mixture was stirred, under argon atmosphere, at room temperature for 15 minutes. To the mixture was added chloroacetone (0.45 ml), and the mixture was stirred at 150° C. overnight (14 hours). The reaction solution was cooled and concentrated under reduced pressure. To the residue was added ice-water, and the mixture was extracted with ethyl acetate. The upper layer was washed with saturated brine, dried (anhydrous magnesium sulfate), and concentrated under reduced pressure, and the residue was subjected to silica gel chromatography and eluted with ethyl acetate/hexane to give 6-(2-methoxyphenyl)-3-methyl-4,5,6,7-tetrahydrobenzofuran-4-one (0.20 g). the mixture was stirred at 150° C. overnight (14 hours) The reaction solution was cooled concentrated under reduced pressure To the residue was added ice-water the mixture was extracted with ethyl acetate The upper layer was washed with saturated brine dried (anhydrous magnesium sulfate) concentrated under reduced pressure eluted with ethyl acetate/hexane