3,3-dimethylpentanedioic acid

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

Procedure: 40 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, are dissolved in 400 ml of tetrahydrofuran. 2 g of 5% palladium-on-charcoal and 22.8 ml of 2,6-lutidine are added and the mixture is hydrogenated at normal pressure and room temperature. When the absorption of hydrogen has ceased, the catalyst is filtered off and the solvent is evaporated off under vacuum. The residue is taken up with water and extracted with ether. The ether phase is washed with a dilute solution of hydrochloric acid in the cold, washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate and evaporated under vacuum to give, after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C. is hydrogenated at normal pressure and room temperature When the absorption of hydrogen the catalyst is filtered off the solvent is evaporated off under vacuum extracted with ether The ether phase is washed with a dilute solution of hydrochloric acid in the cold washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate evaporated under vacuum to give after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C.

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

Procedure: 40 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, are dissolved in 400 ml of tetrahydrofuran. 2 g of 5% palladium-on-charcoal and 22.8 ml of 2,6-lutidine are added and the mixture is hydrogenated at normal pressure and room temperature. When the absorption of hydrogen has ceased, the catalyst is filtered off and the solvent is evaporated off under vacuum. The residue is taken up with water and extracted with ether. The ether phase is washed with a dilute solution of hydrochloric acid in the cold, washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate and evaporated under vacuum to give, after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C. is hydrogenated at normal pressure and room temperature When the absorption of hydrogen the catalyst is filtered off the solvent is evaporated off under vacuum extracted with ether The ether phase is washed with a dilute solution of hydrochloric acid in the cold washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate evaporated under vacuum to give after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 139.2 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, in 125 ml of chloroform, stabilized with amylene, is added dropwise, at a temperature of between 5° C. and 10° C., to a solution of 72.8 g of orthophenylenediamine and 112 ml of triethylamine in 1 l of anhydrous tetrahydrofuran. The mixture is stirred at 0° C. for two hours and then at 50° C. for one hour; the crystals are filtered off and the solvents are evaporated off under vacuum. The residue is taken up in 4.4 l of ethanol and 444 l of concentrated hydrochloric acid and the mixture is refluxed for 12 hours. The solvents are evaporated off and the residue is taken up with water and then neutralized with a 1N solution of sodium hydroxide and extracted with ether. The ether phase is dried and then evaporated under vacuum to give 99 g of ethyl 4-(benzimidazol-2-yl)-3,3-dimethylbutanoate in the form of crystals melting at 123° C. at 50° C. for one hour the crystals are filtered off the solvents are evaporated off under vacuum 444 l of concentrated hydrochloric acid and the mixture is refluxed for 12 hours The solvents are evaporated off extracted with ether The ether phase is dried evaporated under vacuum

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

Procedure: 10 g of 2-(4-chlorobenzylamino)-5-fluoroaniline, prepared in Example 8, are dissolved in 100 ml of chloroform, stabilized with amylene, and 6 ml of triethylamine. A solution of 8.25 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, in 20 ml of chloroform, stabilized with amylene, is added dropwise. The mixture is stirred for two hours at room temperature, the crystals formed rae filtered off and the solvents are evaporated off under vacuum. The residue obtained is dissolved in 200 ml of ethanol and 30 ml of concentrated hydrochloric acid and the mixture is refluxed for 10 hours. The solvents are evaporated off to dryness and the residue is taken up with water and then extracted with ethyl acetate. The organic phase is dried and evaporated under vacuum to give 14 g of ethyl 4-[1-(4-chlorobenzyl)-5-fluorobenzimidazol-2-yl]-3,3-dimethylbutanoate in the form of an oil, which is used as such for the next step. is added dropwise the crystals formed rae filtered off the solvents are evaporated off under vacuum The residue obtained The solvents are evaporated off to dryness extracted with ethyl acetate The organic phase is dried evaporated under vacuum

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

Procedure: 40 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, are dissolved in 400 ml of tetrahydrofuran. 2 of 5% palladium-on-charcoal and 22.8 ml of 2,6-lutidine are added and the mixture is hydrogenated at normal pressure and room temperature. When the absorption of hydrogen has ceased, the catalyst is filtered off and the solvent is evaporated off under vacuum. The residue is taken up with water and extracted with ether. The ether phase is washed with a dilute solution of hydrochloric acid in the cold, washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate and evaporated under vacuum to give, after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C. is hydrogenated at normal pressure and room temperature When the absorption of hydrogen the catalyst is filtered off the solvent is evaporated off under vacuum extracted with ether The ether phase is washed with a dilute solution of hydrochloric acid in the cold washed with a solution of sodium bicarbonate in the cold, dried over magnesium sulfate evaporated under vacuum to give after distillation of the residue, 18 g of ethyl 4-formyl-3,3-dimethylbutanoate in the form of a liquid with a boiling point b.p.20 of 112°-118° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 139.2 of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, in 125 ml of chloroform, stabilized with amylene, is added dropwise, at a temperature of between 5° C. and 10° C., to a solution of 72.8 g of orthophenylenediamine and 112 ml of triethylamine in 1 l of anhydrous tetrahydrofuran. The mixture is stirred at 0° C. for two hours and then at 50° C. for one hour; the crystals are filtered off and the solvents are evaporated off under vacuum. The residue is taken up in 4.4 1 of ethanol and 444 ml of concentrated hydrochloric acid and the mixture is refluxed for 12 hours. The solvents are evaporated off and the residue is taken up with water and then neutralized with a 1 N solution of sodium hydroxide and extracted with ether. The ether phase is dried and then evaporated under vacuum to give 99 g of ethyl 4-(benzimidazol-2-yl)-3,3-dimethylbutanoate in the form of crystals melting at 123° C. at 50° C. for one hour the crystals are filtered off the solvents are evaporated off under vacuum the mixture is refluxed for 12 hours The solvents are evaporated off extracted with ether The ether phase is dried evaporated under vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 139.2 of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, in 125 ml of chloroform, stabilized with amylene, is added dropwise, at a temperature of between 5° C. and 10° C., to a solution of 72.8 g of orthophenylenediamine and 112 ml of triethylamine in 1 l of anhydrous tetrahydrofuran. The mixture is stirred at 0° C. for two hours and then at 50° C. for one hour; the crystals are filtered off and the solvents are evaporated off under vacuum. The residue is taken up in 4.4 1 of ethanol and 444 ml of concentrated hydrochloric acid and the mixture is refluxed for 12 hours. The solvents are evaporated off and the residue is taken up with water and then neutralized with a 1 N solution of sodium hydroxide and extracted with ether. The ether phase is dried and then evaporated under vacuum to give 99 g of ethyl 4-(benzimidazol-2-yl)-3,3-dimethylbutanoate in the form of crystals melting at 123° C. at 50° C. for one hour the crystals are filtered off the solvents are evaporated off under vacuum the mixture is refluxed for 12 hours The solvents are evaporated off extracted with ether The ether phase is dried evaporated under vacuum

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

Procedure: 10 g of 2-(4-chlorobenzylamino)-5-fluoroaniline, prepared in Example 8, are dissolved in 100 ml of chloroform, stabilized with amylene, and 6 ml of triethylamine. A solution of 8.25 g of the acid chloride ethyl ester of 3,3-dimethylglutaric acid, prepared in Example 28, in 20 ml of chloroform, stabilized with amylene, is added dropwise. The mixture is stirred for two hours at room temperature, the crystals formed are filtered off and the solvents are evaporated off under vacuum. The residue obtained is dissolved in 200 ml of ethanol and 30 ml of concentrated hydrochloric acid and the mixture is refluxed for 10 hours. The solvents are evaporated off to dryness and the residue is taken up with water and then extracted with ethyl acetate. The organic phase is dried and evaporated under vacuum to give 14 g of ethyl 4-[1-(4-chlorobenzyl)-5-fluorobenzimidazol-2-yl]-3,3-dimethylbutanoate in the form of an oil, which is used as such for the next step. is added dropwise the crystals formed are filtered off the solvents are evaporated off under vacuum The residue obtained The solvents are evaporated off to dryness extracted with ethyl acetate The organic phase is dried evaporated under vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3,3-Dimethylglutaric acid (18.70 g, 116.8 mmol) was dissolved in acetyl chloride (25 mL, 352 mmol), and refluxed for 2 hours. The reaction mixture was evaporated to dryness, and the residue was dissolved in diethyl ether. The ether solution was concentrated on a steam bath, and then cooled to 0° C. for 1 hour. The precipitate was filtered to give the title compound. refluxed for 2 hours The reaction mixture was evaporated to dryness the residue was dissolved in diethyl ether The ether solution was concentrated on a steam bath The precipitate was filtered

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

Procedure: To the solution of 3,3-dimethylglutaric acid (Aldrich) (5.1 g, 32 mmol) in anhydrous tetrahydrofuran (100 mL) at 0° C. was added a solution of BH3.THF (1 M, 100 mL, 100 mmol). The reaction mixture was stirred at room temperature for 18 h. Aqueous HCl solution was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous NaHCO3 solution, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc) to give 3,3-dimethyl-pentane-1,5-diol as a colorless oil (1.5 g, 34%). the mixture was extracted with ethyl acetate The organic layer was separated washed with saturated aqueous NaHCO3 solution, brine dried over MgSO4 concentrated The residue was purified by chromatography (EtOAc)

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

Procedure: The process of the invention converts isophorone into an ozone-addition product, which is then converted into 3,3-dimethyl-5-oxo-hexanoic acid. From the latter, 3,3-dimethylglutaric acid is produced by means of hydrogen peroxide treatment.

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

Procedure: Step A To the solution of 3,3-dimethylglutaric acid (Aldrich) (5.1 g, 32 mmol) in anhydrous tetrahydrofuran (100 mL) at 0° C. was added a solution of BH3.THF (1 M, 100 mL, 100 mmol). The reaction mixture was stirred at room temperature for 18 h. Aqueous HCl solution was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with saturated aqueous NaHCO3 solution, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc) to give 3,3-dimethyl-pentane-1,5-diol as a colorless oil (1.5 g, 34%). the mixture was extracted with ethyl acetate The organic layer was separated washed with saturated aqueous NaHCO3 solution, brine dried over MgSO4 concentrated The residue was purified by chromatography (EtOAc)