(1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carbonyl chloride

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

Procedure: Under ice-water cooling, 350 mg of (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride was added dropwise to the mixed solution of 300 mg of (RS)-2-methyl-4-methylidene-3(2,2,2-trifluoroethyl)cyclopent-2-en-1-ol, 5 mg of 2,6-di-tert-butyl-4-methylphenol, 185 mg of pyridine and 5 mg of 4-dimethylaminopyridine in 10 ml of dry terahydrofuran and then the resultant reaction mixture was allowed to react further 6 hours at room temperature. Then 10 ml of 10% aqueous ammonia solution was added to the solution and vigorously stirred for 2 hours. The reaction mixture was extracted three times with diethyl ether and the ether layers were combined. The combined layer was washed with brine and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was evaporated. The obtained residue was subjected to silica gel column chromatography to afford 280 mg of the desired (RS)-2-methyl-4-methylidene-3-(2,2,2-trifluoroethyl)cyclopent-2-en-1-yl (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylate (Compound No.15). Yield 52% the resultant reaction mixture to react further 6 hours at room temperature The reaction mixture was extracted three times with diethyl ether The combined layer was washed with brine dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was evaporated

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

Procedure: 540 mg of (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid chloride was added under ice-water cooling to a mixed solution of 400 mg of (RS)-2-methyl-4-methylidene-3-ethylcyclopent-2-en-1-ol, 5 mg of 2,6-di-t-butyl-4-methylphenol and 274 mg of pyridine in 6 ml of toluene. The reaction was allowed to react at an ambient temperature for eight hours. The reaction solution was added to a 5% citric acid solution under ice-water cooling and extracted three times with diethyl ether. The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution and a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the obtained residue was subjected to silica gel column chromatography to yield 751 mg of (RS)-2-methyl-4-methylidene-3-ethyl-2-cyclopenten-1-yl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (Compound No.1). Yield 72% (Eluent: n-hexane/ethyl acetate=30/1, 2,6-di-t-butyl-4-methylphenol 0.1%) to react at an ambient temperature for eight hours extracted three times with diethyl ether The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution a saturated sodium chloride solution and dried over anhydrous magnesium sulfate After removal of the solvent under reduced pressure

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

Procedure: 540 mg of (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid chloride was added under ice-water cooling to a mixed solution of 400 mg of (RS)-2-methyl-4-methylidene-3-ethylcyclopent-2-en-1-ol, 5 mg of 2,6-di-t-butyl-4-methylphenol and 274 mg of pyridine in 6 ml of toluene. The reaction was allowed to react at an ambient temperature for eight hours. The reaction solution was added to a 5% citric acid solution under ice-water cooling and extracted three times with diethyl ether. The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution and a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the obtained residue was subjected to silica gel column chromatography to yield 751 mg of (RS)-2-methyl-4-methylidene-3-ethyl-2-cyclopenten-1-yl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (Compound No.1). Yield 72% (Eluent: n-hexane/ethyl acetate=30/1, 2,6-di-t-butyl-4-methylphenol 0.1%) to react at an ambient temperature for eight hours extracted three times with diethyl ether The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution a saturated sodium chloride solution and dried over anhydrous magnesium sulfate After removal of the solvent under reduced pressure

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

Procedure: To a mixture of (RS)-3-(2-propenyl)-3-cyclopenten-1-ol (115 mg), 2,6-di-tert-butyl-4-methylphenol (5 mg), pyridine (5 mg) and toluene (5 ml), (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarbonyl chloride (171 mg) was added under ice-cooling. The resulting reaction mixture was further allowed to react for 8 hours at room temperature. Then the reaction mixture was subjected to the same post-treatment as in Example 1 to afford 165 mg of (RS)-3-(2-propenyl)-3-cyclopenten-1-yl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (Compound No. 41). Yield 65% DD27 1.4895 was added under ice- cooling The resulting reaction mixture to react for 8 hours at room temperature

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

Procedure: To a mixture of (RS)-3-(2-propenyl)-4-methyl-3-cyclopenten-1-ol (190 mg), 2,6-di-tert-butyl-4-methylphenol (5 mg), pyridine (140 mg) and toluene (10 ml), (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropanecarbonyl chloride was added under ice-cooling. The resulting reaction mixture was further allowed to react for 8 hours at room temperature. Then the reaction mixture was subjected to the same post-treatment as in Example 1 to afford 295 mg of (RS)-3-(2-propenyl)-4-methyl-3-cyclopenten-1-yl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (Compound No. 40). Yield 74% nD25 1.4891 was added under ice- cooling The resulting reaction mixture to react for 8 hours at room temperature

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.07 g of (2-phenoxy-5-thiazolyl)-methanol were added to a solution of (1R,3R) 2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane-1-carboxylic acid chloride prepared from 1.68 g of the corresponding acid in 30 ml of benzene and 1.7 ml of pyridine were slowly added thereto at 10° C. The mixture was stirred at 20° C. for 17 hours and was poured into dilute aqueous hydrochloric acid. The decanted aqueous phase was extractedwith ether and the combined organic phases were washed with water, dried and evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with an 8-2 cyclohexane-ethyl acetate mixture to obtain 1.9 g of (2-phenoxy-5-thiazolyl)-methyl (1R,3R) 2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane-1-carboxylate. were slowly added at 10° C the combined organic phases were washed with water dried evaporated to dryness under reduced pressure The residue was chromatographed over silica gel was eluted with an 8-2 cyclohexane-ethyl acetate mixture

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.07 g of (2-phenoxy-5-thiazolyl)-methanol were added to a solution of (1R,3R) 2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane-1-carboxylic acid chloride prepared from 1.68 g of the corresponding acid in 30 ml of benzene and 1.7 ml of pyridine were slowly added thereto at 10° C. The mixture was stirred at 20° C. for 17 hours and was poured into dilute aqueous hydrochloric acid. The decanted aqueous phase was extractedwith ether and the combined organic phases were washed with water, dried and evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with an 8-2 cyclohexane-ethyl acetate mixture to obtain 1.9 g of (2-phenoxy-5-thiazolyl)-methyl (1R,3R) 2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane-1-carboxylate. were slowly added at 10° C the combined organic phases were washed with water dried evaporated to dryness under reduced pressure The residue was chromatographed over silica gel was eluted with an 8-2 cyclohexane-ethyl acetate mixture

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

Procedure: To a mixture solution of 1.78 g of (2,3,5,6-tetrafluoro-4-methylphenyl)methanol, 0.87 g of pyridine and 20 ml of tetrahydrofuran, 2.06 g of (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic chloride was added under ice-cooling and the mixture was stirred for 8 hours at room temperature. The reaction mixture was poured into about 100 ml of ice-water and extracted with each 100 ml of ethyl acetate twice. The combined ethyl acetate was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude product, which was subjected to silica gel column chromatography (eluent: hexane/ethyl acetate=20/1) to give 2.75 g of (2,3,5,6-tetrafluoro-4-methylphenyl)methyl(1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (yield 87%). cooling extracted with each 100 ml of ethyl acetate twice The combined ethyl acetate was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure to give a crude product, which

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

Procedure: 2.06 Grams of (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid chloride was added to a mixture of 1.78 g of (2,3,5,6-tetrafluoro-4-methylphenyl)methanol, 0.87 g of pyridine and 20 ml of tetrahydrofuran under ice-cooling. The resulting mixture was stirred at room temperature for 8 hours. The reaction mixture was poured into about 100 ml of ice water and extracted twice with 100 ml of ethyl acetate. The combined ethyl acetate layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=20/1) to obtain 2.75 g (yield: 87%) of (2,3,5,6-tetrafluoro-4-methylphenyl)methyl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate. cooling extracted twice with 100 ml of ethyl acetate The combined ethyl acetate layer was washed with a saturated aqueous sodium chloride solution dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=20/1)

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

Procedure: Under ice-water cooling, 350 mg of (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride was added dropwise to the mixed solution of 300 mg of (RS)-2-methyl-4-methylidene-3-(2,2,2-trifluoroethyl)cyclopent-2-en-1-ol, 5 mg of 2,6-di-tert-butyl-4-methylphenol, 185 mg of pyridine and 5 mg of 4-dimethylaminopyridine in 10 ml of dry terahydrofuran and then the resultant reaction mixture was allowed to react further 6 hours at room temperature. Then 10 ml of 10% aqueous ammonia solution was added to the solution and vigorously stirred for 2 hours. The reaction mixture was extracted three times with diethyl ether and the ether layers were combined. The combined layer was washed with brine and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was evaporated. The obtained residue was subjected to silica gel column chromatography to afford 280 mg of the desired (RS)-2-methyl-4-methylidene-3-(2,2,2-trifluoroethyl)cyclopent-2-en-1-yl (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylate (Compound No.15). Yield 52% (Eluent: n-hexane/ethyl acetate=30/1, 2,6-di-tert-butyl-4-methylphenol 0.1% ) nD21 1.4805 the resultant reaction mixture to react further 6 hours at room temperature The reaction mixture was extracted three times with diethyl ether The combined layer was washed with brine dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was evaporated

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

Procedure: 540 mg of (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid chloride was added under ice-water cooling to a mixed solution of 400 mg of (RS)-2-methyl-4-methylidene-3-ethylcyclopent-2-en-1-ol, 5 mg of 2,6-di-t-butyl-4-methylphenol and 274 mg of pyridine in 6 ml of toluene. The reaction was allowed to react at an ambient temperature for eight hours. The reaction solution was added to a 5% citric acid solution under ice-water cooling and extracted three times with diethyl ether. The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution and a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the obtained residue was subjected to silica gel column chromatography to yield 751 mg of (RS)-2-methyl-4-methylidene-3-ethyl-2-cyclopenten-1-yl (1R)-trans-2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylate (Compound No.1). Yield 72% (Eluent: n-hexane/ethyl acetate=30/1, 2,6-di-t-butyl-4-methylphenol 0.1%) nD20.5 1.5070 to react at an ambient temperature for eight hours extracted three times with diethyl ether The combined ether layer was washed successively with a saturated sodium hydrogencarbonate solution a saturated sodium chloride solution and dried over anhydrous magnesium sulfate After removal of the solvent under reduced pressure

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

Procedure: Under ice-water cooling, 350 mg of (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride was added dropwise to the mixed solution of 300 mg of (RS)-2-methyl-4-methylidene-3(2,2,2-trifluoroethyl)cyclopent-2-en-1-ol, 5 mg of 2,6-di-tert-butyl-4-methylphenol, 185 mg of pyridine and 5 mg of 4-dimethylaminopyridine in 10 ml of dry terahydrofuran and then the resultant reaction mixture was allowed to react further 6 hours at room temperature. Then 10 ml of 10% aqueous ammonia solution was added to the solution and vigorously stirred for 2 hours. The reaction mixture was extracted three times with diethyl ether and the ether layers were combined. The combined layer was washed with brine and dried over anhydrous magnesium sulfate. After removal of the drying agent, the solvent was evaporated. The obtained residue was subjected to silica gel column chromatography to afford 280 mg of the desired (RS)-2-methyl-4-methylidene-3-(2,2,2-trifluoroethyl)cyclopent-2-en-1-yl (1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylate (Compound No.15). Yield 52% the resultant reaction mixture to react further 6 hours at room temperature The reaction mixture was extracted three times with diethyl ether The combined layer was washed with brine dried over anhydrous magnesium sulfate After removal of the drying agent the solvent was evaporated