methyl 10-chloro-10-oxodecanoate

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

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

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

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

Procedure: 4-Methylanisole (732 mg) was dissolved in nitromethane (30 ml) to prepare a solution. Anhydrous lithium perchlorate (3.8 g), methyl 10-chloro-10-oxodecanoate (2 ml), and scandium triflate (300 mg) were added to the solution, and the mixture was stirred at room temperature for 4 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give methyl 10-(2-methoxy-5-methylphenyl)-10-oxo-decanoate (1.6 g, yield 83%). to prepare a solution the mixture was extracted with ethyl acetate The ethyl acetate layer was then washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

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

Procedure: All reactions reported in this invention were carried in oven-dried three-necked, round-bottomed flasks equipped with a Teflon-coated magnetic stirring bar. The reaction flask was purged with nitrogen, and during the entire operation, the reaction was under nitrogen. To a stirred solution of cyclopropanamine (0.615 g, 10.78 mmol) in 25 mL of dried THF, triethylamine (1.20 g, 11.90 mmol) was added in one portion. After the reaction had been cooled to about 0° C., methyl 10-chloro-10-oxodecanoate (2.53 g, 10.78 mmol) in 5 mL of THF was added dropwise via an addition funnel. After the addition, the reaction was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was subjected to roto-vap distillation to remove the majority of solvent, and the residue was poured with stirring into a mixture of ice-water containing 10 mL of HCl aqueous 2N solution (20 mmol) leading to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min, and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was washed with two 50-mL portions of water. The NMR analysis of a dried sample of the material confirmed the structure of the desired ester. The GC retention time of the ester is 12.79 min. The ester was saponified with 20 mL of NaOH aqueous 2N solution (40 mmol) at room temperature overnight. Ice was added to the reaction and acidification with a 30 mL of HCl aqueous 2N solution (60 mmol) led to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min, and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane. The collected solid was dried in vacuo for two days at ambient temperature to afford 1.81 g (70%) of 10-(cyclopropylamino)-10-oxodecanoic acid as a white solid. HPLC: Rt: 3.52 min. 1H NMR (400 MHz DMSO-d6) δ: 0.25 (m, 2H), 0.48 (m, 2H), 1.14 (m, 9H), 1.37 (m, 4H), 1.89 (m, 2H), 2.09 (m, 2H), 7.70 (br. s, 1H), 1.850 (s, 1H). 13C NMR (100 MHz DMSO-d6) δ: 5.60(C2 & C3), 22.0(C8), 24.46(C13), 25.18(C1), 28.63(C9, C10, C11 & C12), 33.64(C14), 35.0(C7), 173.2(C5), 174.45(C15). LC/MS m/z: 242 [(M+1)+]. equipped with a Teflon-coated magnetic stirring bar The reaction flask was purged with nitrogen After the addition to warm to ambient temperature distillation to remove the majority of solvent the residue was poured leading to the immediate precipitation of a white solid Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was washed with two 50-mL portions of water The GC retention time of the ester is 12.79 min led to the immediate precipitation of a white solid Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane The collected solid was dried in vacuo for two days at ambient temperature

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

Procedure: 4-Methylanisole (732 mg) was dissolved in nitromethane (30 ml) to prepare a solution. Anhydrous lithium perchlorate (3.8 g), methyl 10-chloro-10-oxodecanoate (2 ml), and scandium triflate (300 mg) were added to the solution, and the mixture was stirred at room temperature for 4 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give methyl 10-(2-methoxy-5-methylphenyl)-10-oxo-decanoate (1.6 g, yield 83%). to prepare a solution the mixture was extracted with ethyl acetate The ethyl acetate layer was then washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

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

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

Procedure: All reactions reported in this invention were carried in oven-dried three-necked, round-bottomed flasks equipped with a Teflon-coated magnetic stirring bar. The reaction flask was purged with nitrogen, and during the entire operation, the reaction was under nitrogen. To a stirred solution of cyclopropanamine (0.615 g, 10.78 mmol) in 25 mL of dried THF, triethylamine (1.20 g, 11.90 mmol) was added in one portion. After the reaction had been cooled to about 0° C., methyl 10-chloro-10-oxodecanoate (2.53 g, 10.78 mmol) in 5 mL of THF was added dropwise via an addition funnel. After the addition, the reaction was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was subjected to roto-vap distillation to remove the majority of solvent, and the residue was poured with stirring into a mixture of ice-water containing 10 mL of HCl aqueous 2N solution (20 mmol) leading to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min, and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was washed with two 50-mL portions of water. The NMR analysis of a dried sample of the material confirmed the structure of the desired ester. The GC retention time of the ester is 12.79 min. The ester was saponified with 20 mL of NaOH aqueous 2N solution (40 mmol) at room temperature overnight. Ice was added to the reaction and acidification with a 30 mL of HCl aqueous 2N solution (60 mmol) led to the immediate precipitation of a white solid. Stirring was continued for an additional 30 min, and then the precipitation was filtered off with suction through a sintered glass funnel. The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane. The collected solid was dried in vacuo for two days at ambient temperature to afford 1.81 g (70%) of 10-(cyclopropylamino)-10-oxodecanoic acid as a white solid. HPLC: Rt: 3.52 min. 1H NMR (400 MHz DMSO-d6) δ: 0.25 (m, 2H), 0.48 (m, 2H), 1.14 (m, 9H), 1.37 (m, 4H), 1.89 (m, 2H), 2.09 (m, 2H), 7.70 (br. s, 1H), 1.850 (s, 1H). 13C NMR (100 MHz DMSO-d6) δ: 5.60(C2 & C3), 22.0(C8), 24.46(C13), 25.18(C1), 28.63(C9, C10, C11 & C12), 33.64(C14), 35.0(C7), 173.2(C5), 174.45(C15). LC/MS m/z: 242 [(M+1)+]. equipped with a Teflon-coated magnetic stirring bar The reaction flask was purged with nitrogen After the addition to warm to ambient temperature distillation to remove the majority of solvent the residue was poured leading to the immediate precipitation of a white solid Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was washed with two 50-mL portions of water The GC retention time of the ester is 12.79 min led to the immediate precipitation of a white solid Stirring was continued for an additional 30 min the precipitation was filtered off with suction through a sintered glass funnel The collected solid was successively washed with three 50-mL portions of water, and two 25-mL portions of hexane The collected solid was dried in vacuo for two days at ambient temperature

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

Procedure: 4-aminosalicylamide (2 g) from Example 5 is charged with 20 mL of methylene chloride. To the solution, 3.3 g of methyl 10-chloro-10-oxodecanoate is added. The reaction is initiated by addition of 2.6 mL of triethylamine. The reaction mixture is allowed to stir at ambient conditions for 2 days. Solvent is removed and the residue is acidified using 1 N HCl. The precipitate is extracted into ethyl acetate. The organic layer is further extracted with 1 N NaOH and saturated NaCl solutions. After drying over anhydrous sodium sulfate, solvent is removed. The residue is reconstituted in tetrahydrofuran (10 mL) and 10 mL of 2 N NaOH is added. The solution is brought to gentle reflux for 2 hours. The disappearance of the methyl ester is followed by HPLC. When all ester is hydrolyzed, the solution is cooled and acidified and the product is extracted into ethyl acetate. The organic layer is washed with saturated NaCl and dried over anhydrous sodium sulfate. Solvent is removed under reduced pressure and the product is obtained as off-white powder. Solvent is removed The precipitate is extracted into ethyl acetate The organic layer is further extracted with 1 N NaOH and saturated NaCl solutions After drying over anhydrous sodium sulfate, solvent is removed 10 mL of 2 N NaOH is added to gentle reflux for 2 hours the solution is cooled the product is extracted into ethyl acetate The organic layer is washed with saturated NaCl dried over anhydrous sodium sulfate Solvent is removed under reduced pressure the product is obtained as off-white powder

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

Procedure: 4-aminosalicylamide (2 g) from Example 5 is charged with 20 mL of methylene chloride. To the solution, 3.3 g of methyl 10-chloro-10-oxodecanoate is added. The reaction is initiated by addition of 2.6 mL of triethylamine. The reaction mixture is allowed to stir at ambient conditions for 2 days. Solvent is removed and the residue is acidified using 1 N HCl. The precipitate is extracted into ethyl acetate. The organic layer is further extracted with 1 N NaOH and saturated NaCl solutions. After drying over anhydrous sodium sulfate, solvent is removed. The residue is reconstituted in tetrahydrofuran (10 mL) and 10 mL of 2 N NaOH is added. The solution is brought to gentle reflux for 2 hours. The disappearance of the methyl ester is followed by HPLC. When all ester is hydrolyzed, the solution is cooled and acidified and the product is extracted into ethyl acetate. The organic layer is washed with saturated NaCl and dried over anhydrous sodium sulfate. Solvent is removed under reduced pressure and the product is obtained as off-white powder. Solvent is removed The precipitate is extracted into ethyl acetate The organic layer is further extracted with 1 N NaOH and saturated NaCl solutions After drying over anhydrous sodium sulfate, solvent is removed 10 mL of 2 N NaOH is added to gentle reflux for 2 hours the solution is cooled the product is extracted into ethyl acetate The organic layer is washed with saturated NaCl dried over anhydrous sodium sulfate Solvent is removed under reduced pressure the product is obtained as off-white powder

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

Procedure: To a suspension of magnesium (turnings, 17.1 g) in ethyl ether (300 ml), a solution of β-phenethyl bromide (140 g, 0.7 mol) in ethyl ether was added dropwise under mild reflux with vigorous stirring under nitrogen, and stirring was continued for 1 h under reflux. After cooling, the mixture (Grignard reagent) was added dropwise to a solution of 9-carbomethoxynonanoyl chloride (150.1 g, 0.64 mol) in ethyl ether (500 ml) at -50°~-30° C. The mixture was allowed to warm to room temperature, stirred for 2 h at the same temperature and poured into H2O (500 ml). The organic layer was separated, washed with H2O, dried over anhydrous MgSO4 and evaporated in vacuo. The residue (203 g) was chromatographed on silica gel (Wako Gel C-200, manufactured by Wako Pure Chemical Industries, Ltd.) with n-hexane/ethyl acetate (4:1) as eluent to afford the title compound as a colorless oil; yield: 99.7 g. under mild reflux stirring under reflux After cooling stirred for 2 h at the same temperature The organic layer was separated washed with H2O dried over anhydrous MgSO4 evaporated in vacuo The residue (203 g) was chromatographed on silica gel (Wako Gel C-200, manufactured by Wako Pure Chemical Industries, Ltd.) with n-hexane/ethyl acetate (4:1) as eluent

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

Procedure: Thionyl chloride (360 g) was added dropwise to methyl hydrogen sebacate (432.6 g, 2 moles) at 60° C. with vigorous stirring and stirring was continued for 2 h under reflux. The reaction mixture was evaporated and the residue was distilled under reduced pressure to give the title compound as a colorless oil; yield: 400 g; bp 145°-150° C./4 mmHg. (Lit. bp 166°-168° C./14 mmHg; T. D. Heyes, J. C. Roberts, J. Chem. Soc., 1952, 4935). stirring under reflux The reaction mixture was evaporated the residue was distilled under reduced pressure