2,3-dimethylphenol

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:

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

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

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

Procedure: To a solution of 2,3-dimethylphenol (25 g, 204 mmol) in DMSO (205 Ml) was added 4-bromo-butyric acid ethyl ester (40.96 g, 210 mmol) and lithium hydride (2.0 g, 250 mmol) at room temperature. The resulting light brown solution was stirred for 2 days. Then, the reaction mixture was cooled to 0° C. and water (200 Ml) was added slowly. The organic compound was extracted into hexanes (2×200 Ml). The combined organic extracts were washed with brine solution (150 Ml) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage (40L) column chromatography eluting with 5% ethyl acetate in hexanes to isolate 4-(2,3-dimethyl-phenoxy)-butyric acid ethyl ester (45.32 g, 94%) as a colorless oil: ES(+)-HRMS m/e calculated for C14H20O3 (M+)+ 236.1412, found 236.1419. The organic compound was extracted into hexanes (2×200 Ml) The combined organic extracts were washed with brine solution (150 Ml) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5% ethyl acetate in hexanes

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

Procedure: To a solution of 2,3-dimethylphenol (25 g, 204 mmol) in DMSO (205 mL) was added 4-bromo-butyric acid ethyl ester (40.96 g, 210 mmol) and lithium hydride (2.0 g, 250 mmol) at room temperature. The resulting light brown solution was stirred for 2 days. Then, the reaction mixture was cooled to 0° C. and water (200 mL) was added slowly. The organic compound was extracted into hexanes (2×200 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage™ (40 L) column chromatography eluting with 5% ethyl acetate in hexanes to isolate 4-(2,3-dimethyl-phenoxy)-butyric acid ethyl ester (45.32 g, 94%) as a colorless oil: ES(+)-HRMS m/e calculated for C14H20O3 (M+)+ 236.1412, found 236.1419. The organic compound was extracted into hexanes (2×200 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5% ethyl acetate in hexanes

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

Procedure: To a solution of 2,3-dimethylphenol (25 g, 204 mmol) in DMSO (205 mL) was added 4-bromo-butyric acid ethyl ester (40.96 g, 210 mmol) and lithium hydride (2.0 g, 250 mmol) at room temperature. The resulting light brown solution was stirred for 2 days. Then, the reaction mixture was cooled to 0° C. and water (200 mL) was added slowly. The organic compound was extracted into hexanes (2×200 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage™ (40 L) column chromatography eluting with 5% ethyl acetate in hexanes to isolate 4-(2,3-dimethyl-phenoxy)-butyric acid ethyl ester (45.32 g, 94%) as a colorless oil: ES(+)-HRMS m/e calculated for C14H20O3 (M+)+ 236.1412. found 236.1419. The organic compound was extracted into hexanes (2×200 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5% ethyl acetate in hexanes

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

Procedure: 2,3-Dimethylphenol (24.5 g, 0.2 mol) was dissolved in 125 ml of anhydrous ethanol. Seventy five (75) ml of 21 wt % sodium ethoxide solution in ethanol (0.2 mol) was added to the solution. The mixture solution was stirred at room temperature for 10 min. Ethyl 4-bromobutyrate (40 g, 0.205 mol) was then added to the solution. The reaction mixture was refluxed at 80° C. for 24 h. The precipitate was filtered of. The filtrate was then mixed with a solution of sodium hydroxide (10 g, 0.25 mol) in 150 ml of water. The mixture was stirred at 70° C. for about 2 hours, and monitored with HPLC. The mixture was diluted with 150 ml of water and acidified to pH 1. Oily precipitate formed immediately. The precipitate was collected by decanting the supernatant and washed with water twice (100 ml×2). The oily precipitate solidified after being kept in water at room temperature overnight. The reaction mixture was refluxed at 80° C. for 24 h The precipitate was filtered of The mixture was stirred at 70° C. for about 2 hours Oily precipitate formed immediately The precipitate was collected by decanting the supernatant washed with water twice (100 ml×2) after being kept in water at room temperature overnight

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4.8 parts of 1-(tert.-butyl)-3-azetidinol, 6.1 parts of 2,3-xylenol and 1.4 parts of trifluoroacetic acid was heated at 130° C. for 12 hours. The reaction mixture was cooled and dissolved in 100 parts of ether, and the solution was washed three times with 50 parts of 2N-sodium hydroxide aqueous solution and extracted three times with 2N-hydrochloric acid aqueous solution. The extract was washed twice with 50 parts of ether and made alkaline by addition of 2N-sodium hydroxide solution. The extraction was conducted three times with 50 parts of ether, and the extract was condensed and distilled under reduced pressure to yield 3.2 parts of 1-(2',3'-dimethylphenyloxy)-3-(tert.-butylamino)-2-propanol having a melting point of 57° C. and a boiling point of 134°-136° C. under 0.7 mm Hg. The reaction mixture was cooled the solution was washed three times with 50 parts of 2N-sodium hydroxide aqueous solution extracted three times with 2N-hydrochloric acid aqueous solution The extract was washed twice with 50 parts of ether by addition of 2N-sodium hydroxide solution The extraction condensed distilled under reduced pressure

Conditions: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 6.5 parts of 1-(tert.-butyl)-3-azetidinol and 6.7 parts of 2,3-xylenol 0.2 part of potassium hydroxide was added, and the mixture was heated at 155° C. for 20 hours. The reaction mixture was cooled and then dissolved in 100 parts of ether. The solution was washed three times with 50 parts of 2N-sodium hydroxide aqueous solution and extracted three times with 2N-hydrochloric acid aqueous solution. The extract was washed with 50 parts of ether and was made alkaline by adding 2N-sodium hydroxide solution gradually thereto. Then, the ether extraction was conducted three times and the extract was condensed and allowed to stand in a cool place. As a result crystals were formed, which were recrystallized twice from ether to yield 8.3 parts of 1-(2',3'-dimethylphenyloxy)-3-(tert.-butylamino)-2-propanol having a melting point of 57° C. Results of infra-red spectrum analysis and ultraviolet ray absorption analysis of the product are as follows: was added The reaction mixture was cooled The solution was washed three times with 50 parts of 2N-sodium hydroxide aqueous solution extracted three times with 2N-hydrochloric acid aqueous solution The extract was washed with 50 parts of ether by adding 2N-sodium hydroxide solution gradually Then, the ether extraction condensed As a result crystals were formed which were recrystallized twice from ether