2-methyl-4,5-dihydro-1H-imidazole

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Dichloromethane (400 mL), 2-methyl-2-imidazoline (56.38 g, 0.637 mol), and triethylamine (283.51 g, 2.802 mol) are placed in a 2000 mL three-necked round bottomed flask equipped with a reflux condenser, internal thermometer, mechanical stirrer, addition funnel, and argon inlet. The solution is brought to reflux and 15 min later a solution of 6-(N,N-Dimethylamino)hexanoyl chloride-hydrochloride (150 g, 0.700 mol), prepared as described in example II, dissolved in dichloromethane (300 mL) is added dropwise over 45 min. The mixture is refluxed for an additional 2 h before being cooled to room temperature. The salts are filtered and washed with methylene chloride. The combined flitrates are washed with 5% NaHCO3 solution (3×300 mL) and water (300 mL), After drying over MgSO4 and filtration, the organic layer is concentrated first by rotary evaporation at 50° C. and then by Kugelrohr distillation at 60°-70° C. (0.2 mm Hg) to give 95.20 g (66%) of an oil which solidifies on standing. equipped with a reflux condenser internal thermometer, mechanical stirrer, addition funnel, and argon inlet prepared is added dropwise over 45 min The mixture is refluxed for an additional 2 h The salts are filtered washed with methylene chloride The combined flitrates are washed with 5% NaHCO3 solution (3×300 mL) and water (300 mL) After drying over MgSO4 and filtration the organic layer is concentrated first by rotary evaporation at 50° C. by Kugelrohr distillation at 60°-70° C. (0.2 mm Hg)

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

Procedure: To (2′-bromomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester (0.070 g, 0.17 mmol) and 2-methyl-2-imidazoline (0.017 g, 0.18 mmol) in DMF (1 mL) at 0° C. was added sodium hydride (60% in mineral oil; 0.011 g, 0.18 mmol), and the reaction was stirred for 2 hours. After work-up with EtOAc, H2O, and citric acid, the combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound. After work-up with EtOAc, H2O, and citric acid, the combined organic layers were dried over MgSO4 filtered concentrated

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

Procedure: Combine 30.0 gm. (0.16 M) N-(2,6-dimethylphenyl)-2-methylpropenamide [methacroyl-2',6'-xylidide], 13.3 gm. (0.16 M) lysidine, 3 gm. (0.03 M) methanesulphonic acid and 150 ml. of ethanol in a pressure bottle and heat at about 150° C. for about 48 hours. Remove the solvent in vacuo, add 200 ml. of water and adjust the pH to 7.8 with conc. HCl. Extract the aqueous phase with 4×100 ml. of methylene chloride and set these aside. Treat the aqueous phase with 20% NaOH to obtain a pH of about 13. Extract the aqueous phase with 4×100 ml. of methylene chloride. Wash the combined methylene chloride extracts with 3×10 ml. water and dry organic layer over sodium sulfate. Evaporate off the solvents to obtain the title compound. Remove the solvent in vacuo add 200 ml Extract the aqueous phase with 4×100 ml Treat the aqueous phase with 20% NaOH to obtain a pH of about 13 Extract the aqueous phase with 4×100 ml Wash the combined methylene chloride Evaporate off the solvents

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

Procedure: Combine 1.89 gm. (0.01 M) N-(2,6-dimethylphenyl)crotonamide, 0.90 gm. (0.0107 M) lysidine, 0.01 gm. (~0.001 M) methanesulphonic acid and about 40 ml. of ethanol in a pressure bottle and heat (bath temp. 100°-110° C.) for about 100 hours. Remove the solvent in vacuo, add about 50 ml. of water. Adjust the pH to 8.0 with concentrated HCl, and extract the aqueous phase with 2×25 ml. methylene chloride. Then adjust the aqueous phase to pH 13 with 50% sodium hydroxide and extract with 3×30 ml. of methylene chloride. Wash the combined methylene chloride extracts with 2×5 ml. of water. Dry the methylene chloride extracts over sodium sulfate. Evaporate off the solvents to obtain the title compound. Remove the solvent in vacuo add about 50 ml extract the aqueous phase with 2×25 ml extract with 3×30 ml Wash the combined methylene chloride Dry the methylene chloride Evaporate off the solvents

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

Procedure: In a manner similar to Ex. IA react 21.17 gm. (0.1 M) of 2-chloro-2'-ethyl-6'-methylacetanilide and 42.1 gm. (0.5 M) of lysidine in 250 ml. of nitromethane, to obtain the title compound: IA react 21.17 gm

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

Procedure: In a manner similar to Ex. IA react 5.29 gm. (0.025 M) of 3-chloro-2',6'-propionoxylidide with 10.53 gm. (0.125 M) of lysidine in 200 ml. of anhydrous ethanol to obtain the title compound. IA react 5.29 gm

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

Procedure: In a manner similar to Example IA react 15.88 gm. (0.075 M) of 2-chloro-N-(2,6-dimethylphenyl)propionamide with 31.55 gm. (0.375 M) of lysidine in 150 ml. of nitromethane to obtain the title compound.

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

Procedure: To a solution of 10.0 gm. (0.05 M) of 2-chloro-2',6'-acetoxylidide in 100 ml. of nitromethane add 21.35 gm (0.254 M) of lysidine. Stir the solution at room temperature for about 17 hours. Follow the progress of the reaction by thin layer chromatography on silica gel (acetonitrile: ammonium hydroxide: methanol, 85:10:5). At the completion of the reaction, remove the solvent in vacuo, to the residue add 150 ml. of water, adjust the pH to about 7.0 with conc. hydrochloric acid. Extract the resultant solution with 3×100 ml. methylene chloride and discard. Adjust the pH of the water layer to about 11-11.5 with 50% sodium hydroxide. Extract with 4×200 ml. of methylene chloride. Take the combined latter extracts and wash 3×50 ml. of water. Dry the methylene chloride extracts over Na2SO4. Evaporate the solvents to provide the title compound. the progress of the reaction by thin layer chromatography on silica gel (acetonitrile: ammonium hydroxide: methanol, 85:10:5) At the completion of the reaction remove the solvent in vacuo to the residue add 150 ml Extract the resultant solution with 3×100 ml Extract with 4×200 ml wash 3×50 ml Dry the methylene chloride Evaporate the solvents

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

Procedure: Combine 30.0 gm. (0.16 M) N-(2,6-dimethylphenyl)-2-methylpropenamide [methacroyl-2',6'-xylidide], 13.3 gm. (0.16 M) lysidine, 3 gm. (0.03 M) methanesulphonic acid and 150 ml. of ethanol in a pressure bottle and heat at about 150° C. for about 48 hours. Remove the solvent in vacuo, add 200 ml. of water and adjust the pH to 7.8 with conc. HCl. Extract the aqueous phase with 4×100 ml. of methylene chloride and set these aside. Treat the aqueous phase with 20% NaOH to obtain a pH of about 13. Extract the aqueous phase with 4×100 ml. of methylene chloride. Wash the combined methylene chloride extracts with 3×10 ml. water and dry organic layer over sodium sulfate. Evaporate off the solvents to obtain the title compound. Remove the solvent in vacuo add 200 ml Extract the aqueous phase with 4×100 ml Treat the aqueous phase with 20% NaOH to obtain a pH of about 13 Extract the aqueous phase with 4×100 ml Wash the combined methylene chloride Evaporate off the solvents

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

Procedure: Combine 1.89 gm. (0.01 M) N-(2,6-dimethylphenyl)crotonamide, 0.90 gm. (0.0107 M) lysidine, 0.01 gm. (~0.001 M) methanesulphonic acid and about 40 ml. of ethanol in a pressure bottle and heat (bath temp. 100°-110° C.) for about 100 hours. Remove the solvent in vacuo, add about 50 ml. of water. Adjust the pH to 8.0 with concentrated HCl, and extract the aqueous phase with 2×25 ml. methylene chloride. Then adjust the aqueous phase to pH 13 with 50% sodium hydroxide and extract with 3×30 ml. of methylene chloride. Wash the combined methylene chloride extracts with 2×5 ml. of water. Dry the methylene chloride extracts over sodium sulfate. Evaporate off the solvents to obtain the title compound. Remove the solvent in vacuo add about 50 ml extract the aqueous phase with 2×25 ml extract with 3×30 ml Wash the combined methylene chloride Dry the methylene chloride Evaporate off the solvents

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

Procedure: In a manner similar to Ex. IA react 21.17 gm. (0.1 M) of 2-chloro-2'-ethyl-6'-methylacetanilide and 42.1 gm. (0.5 M) of lysidine in 250 ml. of nitromethane, to obtain the title compound: IA react 21.17 gm