ethyl 2-(4-chlorophenyl)-2-oxoacetate

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

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

Procedure: A total of 3.4 mL (10.2 mmol) of 3.0M methylmagnesium iodide was added to a solution of 2.34 g (10 mmol) of ethyl 4-chlorobenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 1.3 g (40% yield) of 5-(4-chlorophenyl)-4-hydroxy-5-methyl-3-phenylmethoxy-2(5H)-furanone as a yellow oil: 1H NMR (CDCl3) δ 7.37-7.21 (m, 9H), 5.10 (s, 2H), 1.73 (s, 3H). to give

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

Procedure: A total of 3.4 mL (10.2 mmol) of 3.0 M methylmagnesium iodide was added to a solution of 2.34 g (10 mmol) of ethyl 4-chlorobenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 1.3 g (40% yield) of 5-(4-chlorophenyl)-4-hydroxy-5-methyl-3-phenylmethoxy-2(5H)-furanone as a yellow oil: 1H NMR (CDCl3) δ 7.37-7.21 (m, 9H), 5.10 (s, 2H), 1.73 (s, 3H). to give

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

Procedure: A total of 3.4 mL (10.2 mmol) of 3.0M methylmagnesium iodide was added to a solution of 2.34 g (10 mmol) of ethyl 4-chlorobenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 1.3 g (40% yield) of 5-(4-chlorophenyl)-4-hydroxy-5-methyl-3-phenylmethoxy-2(5H)-furanone as a yellow oil: 1H NMR (CDCl3) δ 7.37-7.21 (m, 9H), 5.10 (s, 2H), 1.73 (s, 3H). to give

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

Procedure: A total of 3.4 mL (10.2 mmol) of 3.0M methylmagnesium iodide was added to a solution of 2.34 g (10 mmol) of ethyl 4-chlorobenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 1.3 g (40% yield) of 5-(4-chlorophenyl)-4-hydroxy-5-methyl-3-phenylmethoxy-2(5H)-furanone as a yellow oil: 1H NMR (CDCl3) δ 7.37-7.21 (m, 9H), 5.10 (s, 2H), 1.73 (s, 3H). to give

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

Procedure: To a solution of 3-bromopyridine (640 mg) in diethyl ether (10 ml), n-butyl lithium (2.5M-hexane solution, 1.80 ml) was added at −74° C. After 15 minutes' stirring at the same temperature, a solution of ethyl 2-(4-chlorophenyl)-2-oxoacetate (960 mg) in diethyl ether (100 ml) was added. The temperature of the system was raised to room temperature over 30 minutes, and to the reaction solution saturated aqueous ammonium chloride solution was added and extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The organic layer was condensed under reduced pressure, and the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=3/2) to provide ethyl 2-(4-chlorophenyl)-2-hydroxy-2-(3-pyridinyl)acetate (571 mg) as a yellow oily substance. extracted with diethyl ether The organic layer was washed with saturated brine dried over anhydrous sodium sulfate condensed under reduced pressure the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=3/2)

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

Procedure: To a solution of 3-bromopyridine (640 mg) in diethyl ether (10 ml), n-butyl lithium (2.5M-hexane solution, 1.80 ml) was added at −74° C. After 15 minutes' stirring at the same temperature, a solution of ethyl 2-(4-chlorophenyl)-2-oxoacetate (960 mg) in diethyl ether (100 ml) was added. The temperature of the system was raised to room temperature over 30 minutes, and to the reaction solution saturated aqueous ammonium chloride solution was added and extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The organic layer was condensed under reduced pressure, and the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=3/2) to provide ethyl 2-(4-chlorophenyl)-2-hydroxy-2-(3-pyridinyl)acetate (571 mg) as a yellow oily substance. extracted with diethyl ether The organic layer was washed with saturated brine dried over anhydrous sodium sulfate condensed under reduced pressure the resulting residue was purified on silica gel column chromatography (hexane/ethyl acetate=3/2)

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

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

Procedure: The product is obtained by reacting the above diol with ethyl 2-(4-chlorophenyl)-2-oxoacetate according to the method already described, by refluxing in toluene in the presence of para-toluenesulphonic acid. The product is obtained

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

Procedure: 42.5 g (0.2 M) of ethyl 2-oxo-2-(4-chlorophenyl)acetate are placed in 400 ml of CH2Cl2 in a 500 ml reactor. 22.8 g (0.1 M) of 2,2-diphenylpropane-1,3-diol and then 14.2 g (0.1 M) of BF3.Et2O are added. The mixture is left to react with stirring for 72 h at room temperature. The reaction mixture is taken up in NaHCO3 solution. The organic phase is washed with saturated NaCl solution. After drying over Na2SO4 and concentration, a very thick oil is obtained. 150 ml of isopropyl ether are added and a white precipitate forms. After filtration, 30 g of product melting at 156-158° C. are obtained (yield: 71%). The mixture is left to react The organic phase is washed with saturated NaCl solution After drying over Na2SO4 and concentration a very thick oil is obtained After filtration, 30 g of product melting at 156-158° C. are obtained (yield: 71%)

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

Procedure: 4-Chlorobenzoyl cyanide (13.0 g, 0.079 mol) prepared in Example 1a was added to a stirred mixture of sodium bromide (1.0 g, 0.01 mol) and 80% sulphuric acid (10 ml). An exothermic reaction took place with the formation of a solid yellow mass. Ethanol (50 ml) was added and the mixture was heated under reflux to give a yellow solution. On cooling, a colourless precipitate formed. The mixture was diluted with cold water and extracted with isopropyl ether. The organic extract was washed with water, sodium bicarbonate solution and then again with water and dried over sodium sulphate. Evaporation and distillation of the solution gave the product as a yellow oil (8.2 g, 54%)--b.p. 82°-84° C./0.05 mm Hg. An exothermic reaction the mixture was heated under reflux to give a yellow solution On cooling a colourless precipitate formed extracted with isopropyl ether The organic extract was washed with water, sodium bicarbonate solution again with water and dried over sodium sulphate Evaporation and distillation of the solution

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

Procedure: A total of 3.4 mL (10.2 mmol) of 3.0 M methylmagnesium iodide was added to a solution of 2.34 g (10 mmol) of ethyl 4-chlorobenzoylformate in THF in an analogous manner as described for the synthesis of 3,4-dihydroxy-5-methyl-5-phenyl-2(5H)-furanone to give prior to hydrogenolysis 1.3 g (40% yield) of 5-(4-chlorophenyl)-4-hydroxy-5-methyl-3-phenylmethoxy-2(5H)-furanone as a yellow oil: 1H NMR (CDCl3) δ 7.37-7.21 (m, 9H), 5.10 (s, 2H), 1.73 (s, 3H). to give