methyl 4-bromo-3-oxobutanoate

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:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 Grams of 60% sodium hydride was suspended in 150 ml of anhydrous dimethoxyethane and the suspension was cooled to -30° C. Then, 19.4 g of methyl 4-bromoacetoacetate was added dropwise to the suspension and stirred for 1 hour. Further, at the same temperature, an anhydrous dimethoxyethane solution of sodium cinnamy alcoholate prepared from 13.4 g of cinnamyl alcohol, 4 g of 60% of sodium hydride and 75 ml of dimethoxyethane was added dropwise thereto, and the reaction mixture was refluxed for 15 hours. After the reaction mixture was cooled to a room temperature, the reaction mixture was poured into 1N-hydrochloric acid being ice-cooled, and the whole mixture was extracted with ether. The ether extract was washed with water and dried with anhydrous sodium sulfate, and the solvent was removed by evaporation. The residue was purified by means of a silica gel column chromatography (eluent: methanol:dichloromethane=1:20) to yield 6 g of methyl 4(E)-cinnamyloxyacetoacetate Refractive index: nD20 1.5402 was added dropwise the reaction mixture was refluxed for 15 hours After the reaction mixture was cooled to a room temperature cooled the whole mixture was extracted with ether The ether extract was washed with water dried with anhydrous sodium sulfate the solvent was removed by evaporation The residue was purified by means of a silica gel column chromatography (eluent: methanol:dichloromethane=1:20)

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

Procedure: To 150 ml of anhydrous carbon tetrachloride solution containing 116 g of methyl acetoacetate was added dropwise 51 ml of bromine at below 5° C. After the addition was finished the reaction mixture was stirred overnight, then the reaction mixture was poured into ice-water, washed with a diluted sodium carbonate aqueous solution five times, then with a saturated sodium chloride aqueous solution, and dried with anhydrous calcium chloride. The solvent was removed by evaporation to yield 170 g of methyl 4-bromoacetoacetate. After the addition washed with a diluted sodium carbonate aqueous solution five times with a saturated sodium chloride aqueous solution, and dried with anhydrous calcium chloride The solvent was removed by evaporation

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

Procedure: 3,4,5-Trimethoxybenzothioamide (1.0 g) and methyl 4-bromoacetoacetate (858 mg)) were reacted in the same manner in Preparation Example 2 to obtain the title compound.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 22.7 kg of methyl acetoacetate was dissolved in 113.3 kg of 1-chlorobutane and cooled to 0° C. To this mixture was added dropwise 31.4 kg of bromine at 5° C. over 2 hours, and the mixture was thereafter kept at that temperature for 8 hours. The reaction mixture was cooled to −10° C. and added dropwise to 22.7 kg of water at a temperature 10° C. or less in 2 hours, then washed and separated to give an organic layer. The obtained organic layers were concentrated under reduced pressure at a temperature of 40° C. or less to give 42.0 kg of crude methyl 4-bromoacetoacetate. The gas chromatography analysis indicated that the content of methyl 4-bromoacetoacetate in the crude product was 65.3% (27.4 kg, 72% yield), wherein the content of 1-chlorobutane was 19.7%. The reaction mixture was cooled to −10° C. washed separated to give an organic layer The obtained organic layers were concentrated under reduced pressure at a temperature of 40° C. or less

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 2613 g of 1-chlorobutane was dissolved 523 g of methyl acetoacetate and cooled to 0° C. To this mixture was dropwise added 719 g of bromine at 5±5° C. over a period of one hour, and the mixture was thereafter kept at that temperature for four hours. The reaction mixture was washed with 1161 g of a 10% saline solution. After separating the mixture into an aqueous and organic layers, concentration of the organic layer in vacuous at a temperature of 40° C. or less gave 782.9 g of crude methyl 4-bromoacetoacetate. The gas chromatography analysis indicated that the content of methyl 4-bromoacetoacetate in the crude product was 72% (564 g, 64% yield). at 5±5° C. of one hour The reaction mixture was washed with 1161 g of a 10% saline solution After separating the mixture into an aqueous and organic layers, concentration of the organic layer in vacuous at a temperature of 40° C. or less

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

Procedure: To a solution of 22 g of methyl-4-bromoacetoacetate in 200 ml benzene is added 14.4 g of 1,1-dimethylbutylurea and 100 mg of p-toluenesulfonic acid. The solution is heated at reflux under nitrogen for 4 hours with water removal. At the end of this period the solution is cooled and concentrated. The residual material is chromatographed on 400 g of silicic acid. Elution with a solution of benzene (60%), ethyl acetate (30%) and methanol (10%) gives crystalline material. Recrystallization of this material from ethyl acetate gives 1.8 g of 1-(1,1-dimethylbutyl)-3-(2,5-dihydro-5-oxo-3-furyl)urea, m.p. 130°-132°C. The solution is heated At the end of this period the solution is cooled concentrated The residual material is chromatographed on 400 g of silicic acid Elution with a solution of benzene (60%), ethyl acetate (30%) and methanol (10%) gives crystalline material Recrystallization of this material from ethyl acetate

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4 Grams of 60% sodium hydride was suspended in 150 ml of anhydrous dimethoxyethane and the suspension was cooled to -30° C. Then, 19.4 g of methyl 4-bromoacetoacetate was added dropwise to the suspension and stirred for 1 hour. Further, at the same temperature, an anhydrous dimethoxyethane solution of sodium cinnamy alcoholate prepared from 13.4 g of cinnamyl alcohol, 4 g of 60% of sodium hydride and 75 ml of dimethoxyethane was added dropwise thereto, and the reaction mixture was refluxed for 15 hours. After the reaction mixture was cooled to a room temperature, the reaction mixture was poured into 1N-hydrochloric acid being ice-cooled, and the whole mixture was extracted with ether. The ether extract was washed with water and dried with anhydrous sodium sulfate, and the solvent was removed by evaporation. The residue was purified by means of a silica gel column chromatography (eluent: methanol:dichloromethane=1:20) to yield 6 g of methyl 4(E)-cinnamyloxyacetoacetate Refractive index: nD20 1.5402 was added dropwise the reaction mixture was refluxed for 15 hours After the reaction mixture was cooled to a room temperature cooled the whole mixture was extracted with ether The ether extract was washed with water dried with anhydrous sodium sulfate the solvent was removed by evaporation The residue was purified by means of a silica gel column chromatography (eluent: methanol:dichloromethane=1:20)

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

Procedure: To 150 ml of anhydrous carbon tetrachloride solution containing 116 g of methyl acetoacetate was added dropwise 51 ml of bromine at below 5° C. After the addition was finished the reaction mixture was stirred overnight, then the reaction mixture was poured into ice-water, washed with a diluted sodium carbonate aqueous solution five times, then with a saturated sodium chloride aqueous solution, and dried with anhydrous calcium chloride. The solvent was removed by evaporation to yield 170 g of methyl 4-bromoacetoacetate. After the addition washed with a diluted sodium carbonate aqueous solution five times with a saturated sodium chloride aqueous solution, and dried with anhydrous calcium chloride The solvent was removed by evaporation