N,N,2-trimethylpropanamide

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

Procedure: 50.0 g (0.5 mol) of triethylamine in 100 ml of methylene chloride was added dropwise to 350 ml of the solution, prepared according to Example 7a, of the amide chloride of isobutyric acid dimethylamide in methylene chloride at 20° C., while cooling and stirring, and the mixture was then heated and refluxed for 1 hour. Thereafter, 75.0 g (0.55 mol) of zinc chloride were added at 10° C. and 79.0 g (0.5 mol) of 1,1,2-trichlorobutadiene were added dropwise to the reaction solution in the course of 60 minutes. After heating under reflux for 5 hours, 400 ml of water were added to the reaction solution and the mixture was stirred overnight (15 hours). Separating the phases and drying the organic phase over sodium sulphate and subjecting it to fractional distillation gave 10.5 g of 1,1,2-trichlorobutadiene, 11.5 g of isobutryic acid dimethylamine and 66.8 g (59%, relative to isobutyric acid dimethylamine employed) of the ketone of boiling point 112°-117° C./10 mm Hg and refractive index nD20 of 1.509. prepared while cooling the mixture was then heated refluxed for 1 hour After heating under reflux for 5 hours the mixture was stirred overnight (15 hours) Separating the phases drying the organic phase over sodium sulphate to fractional distillation

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

Procedure: To a solution of N,N-dimethyl-2-methylpropionamide (615 mg) in 1,2-dichloroethane (20 mL) at 0° C. was added triflic anhydride (1.51 g) dropwise followed by a solution of 2,4,6-collidine (715 mg) and (E)-1-(methylthio)-4-(2-phenylethenyl)benzene (730 mg, method 1) in 1,2-dichloroethane (5 mL). The mixture was stirred at r.t. for 30 min., heated at reflux for 6 hr, cooled to r.t., and the solvent evaporated. The residue was dissolved in CCl4 (50 mL) and H2O (50 mL) and the mixture refluxed for 18 hr. The organic phase was separated, the aqueous phase extracted with CH2Cl2 (2×), the combined organic phase were dried (MgSO4) and the solvents evaporated. The resulting residue was purified by flash chromatography (silica gel; toluene) to provide title product. heated at reflux for 6 hr cooled to r.t. the solvent evaporated The residue was dissolved in CCl4 (50 mL) H2O (50 mL) and the mixture refluxed for 18 hr The organic phase was separated the aqueous phase extracted with CH2Cl2 (2×) the combined organic phase were dried (MgSO4) the solvents evaporated The resulting residue was purified by flash chromatography (silica gel; toluene)

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

Procedure: To a solution of N,N-dimethyl-2-methylpropionamide (615 mg) in 1,2-dichloroethane (20 mL) at 0° C. was added triflic anhydride (1.51 g) dropwise followed by a solution of 2,4,6-collidine (715 mg) and (E)-1-(methylthio)-4-(2-phenylethenyl)benzene (730 mg, method 1) in 1,2-dichloroethane (5 mL). The mixture was stirred at r.t. for 30 min., heated at reflux for 6 hr, cooled to r.t., and the solvent evaporated. The residue was dissolved in CCl4 (50 mL) and H2O (50 mL) and the mixture refluxed for 18 hr. The organic phase was separated, the aqueous phase extracted with CH2Cl2 (2×), the combined organic phase were dried (MgSO4) and the solvents evaporated. The resulting residue was purified by flash chromatography (silica gel; toluene) to provide title product. heated at reflux for 6 hr cooled to r.t. the solvent evaporated The residue was dissolved in CCl4 (50 mL) H2O (50 mL) and the mixture refluxed for 18 hr The organic phase was separated the aqueous phase extracted with CH2Cl2 (2×) the combined organic phase were dried (MgSO4) the solvents evaporated The resulting residue was purified by flash chromatography (silica gel; toluene)

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

Procedure: 50.0 g (0.5 mol) of triethylamine in 100 ml of methylene chloride was added dropwise to 350 ml of the solution, prepared according to Example 7a, of the amide chloride of isobutyric acid dimethylamide in methylene chloride at 20° C., while cooling and stirring, and the mixture was then heated and refluxed for 1 hour. Thereafter, 75.0 g (0.55 mol) of zinc chloride were added at 10° C. and 79.0 g (0.5 mol) of 1,1,2-trichlorobutadiene were added dropwise to the reaction solution in the course of 60 minutes. After heating under reflux for 5 hours, 400 ml of water were added to the reaction solution and the mixture was stirred overnight (15 hours). Separating the phases and drying the organic phase over sodium sulphate and subjecting it to fractional distillation gave 10.5 g of 1,1,2-trichlorobutadiene, 11.5 g of isobutryic acid dimethylamine and 66.8 g (59%, relative to isobutyric acid dimethylamine employed) of the ketone of boiling point 112°-117° C./10 mm Hg and refractive index nD20 of 1.509. prepared while cooling the mixture was then heated refluxed for 1 hour After heating under reflux for 5 hours the mixture was stirred overnight (15 hours) Separating the phases drying the organic phase over sodium sulphate to fractional distillation

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

Procedure: 50.0 g (0.5 mol) of triethylamine in 100 ml of methylene chloride was added dropwise to 350 ml of the solution, prepared according to Example 7a, of the amide chloride of isobutyric acid dimethylamide in methylene chloride at 20° C., while cooling and stirring, and the mixture was then heated and refluxed for 1 hour. Thereafter, 75.0 g (0.55 mol) of zinc chloride were added at 10° C. and 79.0 g (0.5 mol) of 1,1,2-trichlorobutadiene were added dropwise to the reaction solution in the course of 60 minutes. After heating under reflux for 5 hours, 400 ml of water were added to the reaction solution and the mixture was stirred overnight (15 hours). Separating the phases and drying the organic phase over sodium sulphate and subjecting it to fractional distillation gave 10.5 g of 1,1,2-trichlorobutadiene, 11.5 g of isobutryic acid dimethylamine and 66.8 g (59%, relative to isobutyric acid dimethylamine employed) of the ketone of boiling point 112°-117° C./10 mm Hg and refractive index nD20 of 1.509. prepared while cooling the mixture was then heated refluxed for 1 hour After heating under reflux for 5 hours the mixture was stirred overnight (15 hours) Separating the phases drying the organic phase over sodium sulphate to fractional distillation

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trifluoroacetic anhydride (25 g, 0.09 mol) was added portionwise over a period of 10 minutes at −10° C., to a solution of N,N-dimethyl-isobutyramide (9.16 g) in DCM (100 mL). The resulting mixture was stirred at −10° C. for 10 minutes and then a viscous solution of 4-methylstyrene (8.2 g) and collidine (11.9 mL) in DCM (15 mL) was added portionwise at −10° C. The resulting mixture was heated at reflux for 22 hours then cooled and concentrated under reduced pressure. The oil residue was washed with ethyl ether and the organic phase was decanted away. DCM (75 mL) and water (75 mL) were added to the oil and the mixture was heated at 100° C. for 6 hours. The mixture was cooled to room temperature, separated, and the aqueous layer was extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane) to give 6.45 g (50% yield) of 2,2-dimethyl-3-p-tolyl-cyclobutanone as a yellow oil. The resulting mixture was heated at reflux for 22 hours then cooled concentrated under reduced pressure The oil residue was washed with ethyl ether the organic phase was decanted away DCM (75 mL) and water (75 mL) were added to the oil the mixture was heated at 100° C. for 6 hours The mixture was cooled to room temperature separated the aqueous layer was extracted with DCM The combined organic extracts were dried over Na2SO4 filtered evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trifluoroacetic anhydride (25 g, 0.09 mol) was added portionwise over a period of 10 minutes at −10° C., to a solution of N,N-dimethyl-isobutyramide (9.16 g) in DCM (100 mL). The resulting mixture was stirred at −10° C. for 10 minutes and then a viscous solution of 4-methylstyrene (8.2 g) and collidine (11.9 mL) in DCM (15 mL) was added portionwise at −10° C. The resulting mixture was heated at reflux for 22 hours then cooled and concentrated under reduced pressure. The oil residue was washed with ethyl ether and the organic phase was decanted away. DCM (75 mL) and water (75 mL) were added to the oil and the mixture was heated at 100° C. for 6 hours. The mixture was cooled to room temperature, separated, and the aqueous layer was extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane) to give 6.45 g (50% yield) of 2,2-dimethyl-3-p-tolyl-cyclobutanone as a yellow oil. The resulting mixture was heated at reflux for 22 hours then cooled concentrated under reduced pressure The oil residue was washed with ethyl ether the organic phase was decanted away DCM (75 mL) and water (75 mL) were added to the oil the mixture was heated at 100° C. for 6 hours The mixture was cooled to room temperature separated the aqueous layer was extracted with DCM The combined organic extracts were dried over Na2SO4 filtered evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trifluoroacetic anhydride (25 g, 0.09 mol) was added portionwise over a period of 10 minutes at −10° C., to a solution of N,N-dimethyl-isobutyramide (9.16 g) in DCM (100 mL). The resulting mixture was stirred at −10° C. for 10 minutes and then a viscous solution of 4-methylstyrene (8.2 g) and collidine (11.9 mL) in DCM (15 mL) was added portionwise at −10° C. The resulting mixture was heated at reflux for 22 hours then cooled and concentrated under reduced pressure. The oil residue was washed with ethyl ether and the organic phase was decanted away. DCM (75 mL) and water (75 mL) were added to the oil and the mixture was heated at 100° C. for 6 hours. The mixture was cooled to room temperature, separated, and the aqueous layer was extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane) to give 6.45 g (50% yield) of 2,2-dimethyl-3-p-tolyl-cyclobutanone as a yellow oil. The resulting mixture was heated at reflux for 22 hours then cooled concentrated under reduced pressure The oil residue was washed with ethyl ether the organic phase was decanted away DCM (75 mL) and water (75 mL) were added to the oil the mixture was heated at 100° C. for 6 hours The mixture was cooled to room temperature separated the aqueous layer was extracted with DCM The combined organic extracts were dried over Na2SO4 filtered evaporated under reduced pressure to give 35 g of crude oil, which was purified by flash chromatography (5% to 50% of EtOAc in hexane)

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

Procedure: 34.0 g (0.5 mol) of isoprene and then, at 0°-10° C., 75.0 g (0.55 mol) of zinc chloride were added to 350 ml of the solution, prepared according to Example 1, of the amide chloride is isobutyric acid dimethylamide in methylene chloride, while cooling and stirring. Thereafter, 50.0 g (0.5 mol) of triethylamine were added dropwise at the same temperature and, after warming to 20°-25° C., the mixture was heated to reflux and worked up according to Example 2. This gave 40.4 g (58%, relative to isobutyric acid dimethylamide employed) of the ketone of boiling point 109°-110° C./100 mm Hg and nD20 of 1.4518 (contaminated to the extent of about 10% by 2,2,3-trimethyl-3-vinyl-cyclobutanone). prepared while cooling after warming to 20°-25° C. the mixture was heated to reflux

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

Procedure: To a solution of N,N-dimethyl-2-methylpropionamide (615 mg) in 1,2-dichloroethane (20 mL) at 0° C. was added triflic anhydride (1.51 g) dropwise followed by a solution of 2,4,6-collidine (715 mg) and (E)-1-(methylthio)-4-(2-phenylethenyl)benzene (730 mg, method 1) in 1,2-dichloroethane (5 mL). The mixture was stirred at r.t. for 30 min., heated at reflux for 6 hr, cooled to r.t., and the solvent evaporated. The residue was dissolved in CCl4 (50 mL) and H2O (50 mL) and the mixture refluxed for 18 hr. The organic phase was separated, the aqueous phase extracted with CH2Cl2 (2×), the combined organic phase were dried (MgSO4) and the solvents evaporated. The resulting residue was purified by flash chromatography (silica gel; toluene) to provide title product. heated at reflux for 6 hr cooled to r.t. the solvent evaporated The residue was dissolved in CCl4 (50 mL) H2O (50 mL) and the mixture refluxed for 18 hr The organic phase was separated the aqueous phase extracted with CH2Cl2 (2×) the combined organic phase were dried (MgSO4) the solvents evaporated The resulting residue was purified by flash chromatography (silica gel; toluene)