1-(bromomethyl)-3-(difluoromethoxy)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 6.81 g (0.03 mol) of 3-difluoromethoxy-benzyl bromide and 6.27 g (0.03 mol) of 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylic acid were dissolved in 150 ml of toluene, 0.5 g of tetrabutylammonium bromide and 2 g of powdered KOH (industrial product, 87% pure) were added and the mixture was heated to the boil for 2-3 hours. After cooling, the reaction mixture was poured into 150 ml of water, the toluene phase was separated off, washed with 100 ml of water and dried with sodium sulphate and the toluene was distilled off in vacuo. Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg. 8.3 g (78% of theory) of 3-difluoromethoxy-benzyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylate were obtained as a viscous oil with the refractive index hD20 =1.5110. the mixture was heated to the boil for 2-3 hours After cooling the toluene phase was separated off washed with 100 ml of water dried with sodium sulphate the toluene was distilled off in vacuo Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg

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

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 5-(2,6-dimethoxyphenyl)-3-methylpyrrolidin-2-one with commercially available 1-(bromomethyl)-3-(difluoromethoxy)benzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions F): tR=0.84 min.; [M+H]+: 392.16 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

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

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with commercially available 1-(bromomethyl)-3-(difluoromethoxy)benzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions D): tR=1.05 min.; [M+H]+: 392.75 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

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

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with commercially available 1-(bromomethyl)-3-(difluoromethoxy)benzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions D): tR=1.05 min.; [M+H]+: 392.75 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

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

実験手順: 6.81 g (0.03 mol) of 3-difluoromethoxy-benzyl bromide and 6.27 g (0.03 mol) of 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylic acid were dissolved in 150 ml of toluene, 0.5 g of tetrabutylammonium bromide and 2 g of powdered KOH (industrial product, 87% pure) were added and the mixture was heated to the boil for 2-3 hours. After cooling, the reaction mixture was poured into 150 ml of water, the toluene phase was separated off, washed with 100 ml of water and dried with sodium sulphate and the toluene was distilled off in vacuo. Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg. 8.3 g (78% of theory) of 3-difluoromethoxy-benzyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylate were obtained as a viscous oil with the refractive index nD20 =1.5110. the mixture was heated to the boil for 2-3 hours After cooling the toluene phase was separated off washed with 100 ml of water dried with sodium sulphate the toluene was distilled off in vacuo Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg

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

実験手順: 6.81 g (0.03 mol) of 3-difluoromethoxy-benzyl bromide and 6.27 g (0.03 mol) of 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylic acid were dissolved in 150 ml of toluene, 0.5 g of tetrabutylammonium bromide and 2 g of powdered KOH (industrial product, 87% pure) were added and the mixture was heated to the boil for 2-3 hours. After cooling, the reaction mixture was poured into 150 ml of water, the toluene phase was separated off, washed with 100 ml of water and dried with sodium sulphate and the toluene was distilled off in vacuo. Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg. 8.3 g (78% of theory) of 3-difluoromethoxy-benzyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylate were obtained as a viscous oil with the refractive index nD20 =1.5110. the mixture was heated to the boil for 2-3 hours After cooling the toluene phase was separated off washed with 100 ml of water dried with sodium sulphate the toluene was distilled off in vacuo Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg

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

実験手順: N-(Diphenylmethylene)Glycine ethyl ester (500 mg, 1.87 mmol), Tetrabuylammonium Bromide (63 mg, 0.187 mmol) and 3-(Difluoromethoxy)benzyl bromide (0.5 mL, 1.87 mmol) were placed in a flask. The flask was evacuated and backfilled with argon. Anhyd dichloromethane was added to the flask, and the reaction was cooled in dry-ice acetone bath to −78° C. 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (0.7 mL, 2.44 mmol) was added slowly under argon at −78° C. The reaction was allowed to stir at −78° C. for 30 minutes, and then warmed to room temperature over 16 h. The solvent was removed under vacuum. The residue was pre-adsorbed on to SiO2 and the product was isolated via SiO2 to yield 700 mg of light yellow oil. MS 424.0 (M+H)+. The flask was evacuated Anhyd dichloromethane was added to the flask warmed to room temperature over 16 h The solvent was removed under vacuum the product was isolated via SiO2

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

実験手順: 6.81 g (0.03 mol) of 3-difluoromethoxy-benzyl bromide and 6.27 g (0.03 mol) of 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylic acid were dissolved in 150 ml of toluene, 0.5 g of tetrabutylammonium bromide and 2 g of powdered KOH (industrial product, 87% pure) were added and the mixture was heated to the boil for 2-3 hours. After cooling, the reaction mixture was poured into 150 ml of water, the toluene phase was separated off, washed with 100 ml of water and dried with sodium sulphate and the toluene was distilled off in vacuo. Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg. 8.3 g (78% of theory) of 3-difluoromethoxy-benzyl 2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropanecarboxylate were obtained as a viscous oil with the refractive index hD20 =1.5110. the mixture was heated to the boil for 2-3 hours After cooling the toluene phase was separated off washed with 100 ml of water dried with sodium sulphate the toluene was distilled off in vacuo Last residues of solvent were removed by incipient distillation at a bath temperature of 60°-80° C./0.2 to 1 mm Hg

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

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 5-(2,6-dimethoxyphenyl)-3-methylpyrrolidin-2-one with commercially available 1-(bromomethyl)-3-(difluoromethoxy)benzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions F): tR=0.84 min.; [M+H]+: 392.16 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

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

実験手順: Prepared according to the described general procedure 4 (GP4) by reaction of 6-(2,6-dimethoxyphenyl)piperidin-2-one with commercially available 1-(bromomethyl)-3-(difluoromethoxy)benzene. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions D): tR=1.05 min.; [M+H]+: 392.75 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound