methyl 2-cyclopropylideneacetate

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 45.69 g (222.2 mmol) of copper(I) bromide/dimethyl sulfide complex and 9.42 g (222.2 mmol) of anhydrous lithium chloride were dissolved in 300 ml of THF, the mixture was cooled to −78° C. and 100 ml (200 mmol) of a 2 M solution of allylmagnesium bromide in diethyl ether were added slowly. 28.2 ml (222.2 mmol) of chlorotrimethylsilane and 11.21 g (100 mmol) of methyl cyclopropylideneacetate [CAS Registry No. 110793-87-8] were then added dropwise in succession to the reaction solution, and the mixture was stirred for about 5 min (monitored by TLC, mobile phase cyclohexane/ethyl acetate 20:1). 50 ml of an aqueous solution of ammonia/ammonium chloride (1:9) were then added, and the reaction solution was filtered through kieselguhr. The organic phase was separated off and the aqueous phase was extracted two more times with diethyl ether. The combined organic phases were then washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in 100 ml of THF, and 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added. The reaction solution was stirred for another 10 min and then concentrated to dryness. The crude product obtained was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 6.92 g (45 mmol, 45% of theory) of the title compound. 110793-87-8] were then added dropwise in succession to the reaction solution the reaction solution was filtered through kieselguhr The organic phase was separated off the aqueous phase was extracted two more times with diethyl ether The combined organic phases were then washed with saturated sodium chloride solution dried over magnesium sulfate concentrated under reduced pressure The residue was dissolved in 100 ml of THF 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added concentrated to dryness

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 ml (1.70 mol) of diisopropylamine were dissolved in 700 ml of abs. THF, the mixture was cooled to −40° C. and 681 ml (1.7 mol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The solution was stirred at −40° C. for 30 min and then cooled to −78° C., and a solution of 166.6 ml (1.7 mol) of ethyl acetate p.a. in 200 ml of abs. THF was added. After the end of the addition, the mixture was stirred at −78° C. for another 30 min 159 g (crude product, about 1.42 mol) of methyl cyclopropylideneacetate, dissolved in a little abs. THF, were then added dropwise. The reaction mixture was stirred at −78° C. for 1 h and then, via −40° C., slowly warmed to about 0° C., and a saturated aqueous ammonium chloride solution was finally added. The mixture was extracted with ethyl acetate and the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1). This gave 109.5 g of the target compound which was contaminated by the diethyl ester derivative and was not purified any further. cooled to −78° C. After the end of the addition dissolved in a little abs The reaction mixture was stirred at −78° C. for 1 h via −40° C., slowly warmed to about 0° C. The mixture was extracted with ethyl acetate the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution dried over sodium sulphate concentrated under reduced pressure The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1) was not purified any further

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 ml (1.70 mol) of diisopropylamine were dissolved in 700 ml of abs. THF, the mixture was cooled to −40° C. and 681 ml (1.7 mol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The solution was stirred at −40° C. for 30 min and then cooled to −78° C., and a solution of 166.6 ml (1.7 mol) of ethyl acetate p.a. in 200 ml of abs. THF was added. After the end of the addition, the mixture was stirred at −78° C. for another 30 min 159 g (crude product, about 1.42 mol) of methyl cyclopropylideneacetate, dissolved in a little abs. THF, were then added dropwise. The reaction mixture was stirred at −78° C. for 1 h and then, via −40° C., slowly warmed to about 0° C., and a saturated aqueous ammonium chloride solution was finally added. The mixture was extracted with ethyl acetate and the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1). This gave 109.5 g of the target compound which was contaminated by the diethyl ester derivative and was not purified any further. cooled to −78° C. After the end of the addition dissolved in a little abs The reaction mixture was stirred at −78° C. for 1 h via −40° C., slowly warmed to about 0° C. The mixture was extracted with ethyl acetate the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution dried over sodium sulphate concentrated under reduced pressure The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1) was not purified any further

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 45.69 g (222.2 mmol) of copper(I) bromide/dimethyl sulfide complex and 9.42 g (222.2 mmol) of anhydrous lithium chloride were dissolved in 300 ml of THF, the mixture was cooled to −78° C. and 100 ml (200 mmol) of a 2 M solution of allylmagnesium bromide in diethyl ether were added slowly. 28.2 ml (222.2 mmol) of chlorotrimethylsilane and 11.21 g (100 mmol) of methyl cyclopropylideneacetate [CAS Registry No. 110793-87-8] were then added dropwise in succession to the reaction solution, and the mixture was stirred for about 5 min (monitored by TLC, mobile phase cyclohexane/ethyl acetate 20:1). 50 ml of an aqueous solution of ammonia/ammonium chloride (1:9) were then added, and the reaction solution was filtered through kieselguhr. The organic phase was separated off and the aqueous phase was extracted two more times with diethyl ether. The combined organic phases were then washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in 100 ml of THF, and 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added. The reaction solution was stirred for another 10 min and then concentrated to dryness. The crude product obtained was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 6.92 g (45 mmol, 45% of theory) of the title compound. 110793-87-8] were then added dropwise in succession to the reaction solution the reaction solution was filtered through kieselguhr The organic phase was separated off the aqueous phase was extracted two more times with diethyl ether The combined organic phases were then washed with saturated sodium chloride solution dried over magnesium sulfate concentrated under reduced pressure The residue was dissolved in 100 ml of THF 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added concentrated to dryness

反応条件: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon, 112 g (690 mmol) of 1,3,5-trihydroxybenzene dihydrate are dissolved in 230 ml abs. dimethylformamide, 28.82 g (230 mmol) of methyl cyclopropylideneacetate (Example 41A) and 20 g of 4 Å molecular sieve (as powder) are added and the mixture is stirred at a bath temperature of 130° C. overnight. 1 liter of 1 N hydrochloric acid is then added, and the mixture is extracted repeatedly with ethyl acetate. The combined organic phases are washed once with water and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated. 230 ml (2.99 mol) of trifluoroacetic acid are added to the product obtained, and the mixture is heated to 75° C. and stirred for 8 hours. The mixture is then cooled, water is added and the mixture is extracted repeatedly with ethyl acetate. The combined organic phases are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is purified on silica gel (mobile phase: dichloromethane/methanol 100:1→100:3). The product fractions are combined and concentrated. Dichloromethane is added to the residue obtained, the mixture is stirred briefly and the precipitate is filtered off with suction and dried under high vacuum. This gives 2.25 g (5% of theory) of the target compound. The mother liquor is then purified again on a silica gel column (mobile phase: dichloromethane/methanol 100:1). This gives a further 3.41 g (7% of theory) of the title compound. the mixture is extracted repeatedly with ethyl acetate The combined organic phases are washed once with water and once with saturated sodium chloride solution dried over sodium sulfate concentrated obtained the mixture is heated to 75° C. stirred for 8 hours The mixture is then cooled the mixture is extracted repeatedly with ethyl acetate The combined organic phases are washed twice with saturated sodium chloride solution dried over sodium sulfate filtered concentrated The residue is purified on silica gel (mobile phase: dichloromethane/methanol 100:1→100:3) concentrated Dichloromethane is added to the residue obtained the mixture is stirred briefly the precipitate is filtered off with suction dried under high vacuum The mother liquor is then purified again on a silica gel column (mobile phase: dichloromethane/methanol 100:1)

反応条件: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 ml (1.70 mol) of diisopropylamine were dissolved in 700 ml of abs. THF, the mixture was cooled to −40° C. and 681 ml (1.7 mol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The solution was stirred at −40° C. for 30 min and then cooled to −78° C., and a solution of 166.6 ml (1.7 mol) of ethyl acetate p.a. in 200 ml of abs. THF was added. After the end of the addition, the mixture was stirred at −78° C. for another 30 min 159 g (crude product, about 1.42 mol) of methyl cyclopropylideneacetate, dissolved in a little abs. THF, were then added dropwise. The reaction mixture was stirred at −78° C. for 1 h and then, via −40° C., slowly warmed to about 0° C., and a saturated aqueous ammonium chloride solution was finally added. The mixture was extracted with ethyl acetate and the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1). This gave 109.5 g of the target compound which was contaminated by the diethyl ester derivative and was not purified any further. cooled to −78° C. After the end of the addition dissolved in a little abs The reaction mixture was stirred at −78° C. for 1 h via −40° C., slowly warmed to about 0° C. The mixture was extracted with ethyl acetate the organic phase was washed with 1 N hydrochloric acid and sat. sodium chloride solution dried over sodium sulphate concentrated under reduced pressure The residue was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 9:1) was not purified any further

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 45.69 g (222.2 mmol) of copper(I) bromide/dimethyl sulfide complex and 9.42 g (222.2 mmol) of anhydrous lithium chloride were dissolved in 300 ml of THF, the mixture was cooled to −78° C. and 100 ml (200 mmol) of a 2 M solution of allylmagnesium bromide in diethyl ether were added slowly. 28.2 ml (222.2 mmol) of chlorotrimethylsilane and 11.21 g (100 mmol) of methyl cyclopropylideneacetate [CAS Registry No. 110793-87-8] were then added dropwise in succession to the reaction solution, and the mixture was stirred for about 5 min (monitored by TLC, mobile phase cyclohexane/ethyl acetate 20:1). 50 ml of an aqueous solution of ammonia/ammonium chloride (1:9) were then added, and the reaction solution was filtered through kieselguhr. The organic phase was separated off and the aqueous phase was extracted two more times with diethyl ether. The combined organic phases were then washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in 100 ml of THF, and 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added. The reaction solution was stirred for another 10 min and then concentrated to dryness. The crude product obtained was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave 6.92 g (45 mmol, 45% of theory) of the title compound. 110793-87-8] were then added dropwise in succession to the reaction solution the reaction solution was filtered through kieselguhr The organic phase was separated off the aqueous phase was extracted two more times with diethyl ether The combined organic phases were then washed with saturated sodium chloride solution dried over magnesium sulfate concentrated under reduced pressure The residue was dissolved in 100 ml of THF 222 ml (222 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF were added concentrated to dryness