ethyl 3,3-dimethylhexanoate

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:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dimethyl methylphosphonate (11.7 g, 102 mmol) was dissolved in anhydrous THF (200 ml) and the resulting solution was cooled to -78° C. under argon atmosphere. A solution of n-butyl lithium in hexane (1.63N, 62.3 ml, 102 mmol) was added and the mixture was stirred for 30 minutes. A solution of ethyl 3,3-dimethylhexanoate (7.00 g, 40.6 mmol) in anhydrous THF (50 ml) was added to the reaction mixture at -78° C. andthe mixture was stirred for 30 minutes and then at room temperature for further 2 hours. Acetic acid was added to neutralize the solution. Water (20 ml) was added and then the solution was concentrated. The resulting residue were partitioned between ethyl acetate (200 ml) and water (10 ml). The ethyl acetate layer was separated, washed with water (80 ml) and with brine (100 ml), dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled under reduced pressure to give oily product, dimethyl 4,4-dimethyl-2-oxoheptylphosphonate (8.11 g, 32.4 mmol, 79.8%, b.p.: 101°-104° C./0.03 mmHg). The structure was identified by the following data. was stirred for 30 minutes at room temperature for further 2 hours the solution was concentrated The resulting residue were partitioned between ethyl acetate (200 ml) and water (10 ml) The ethyl acetate layer was separated washed with water (80 ml) and with brine (100 ml) dried over anhydrous magnesium sulfate concentrated The residue was distilled under reduced pressure

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

Procedure: To a solution of ethyl 2-ethoxycarbonyl-3,3-dimethylhexanoate (24.5 g, 100 mmol) in ethanol (150 ml), was added aqueous sodium hydroxide solution (1N, 180 ml, 180 mmol) and the mixture was stirred at room temperature for 24 hours and then at 40° C. for additional 2 hours. Aqueous hydrogen chloride (3N, 60 ml, 180 mmol) was added to the reaction mixture and the resulting mixture was then concentrated to 150 ml. The mixture was extracted with ethyl acetate (200 ml) and the aqueous layer was further extracted with ethyl acetate (50 ml×2). The combined organic layers were washed with water (100 ml) and with brine (100 ml), and dried over anhydrous magnesium sulfate. The resulting solution was concentrated and the residue was stirred at 180° C. for 2.5 hours. Ether (30 ml) was added to the reaction mixture. The resulting mixture was then treated with diazomethane. After removing off ether, the residue was further distilled under reduced pressure to give oily product, ethyl 3,3-dimethylhexanoate (11.07 g, 64.4 mmol), 64.4%, b.p.: 87°-94° C./22 mmHg). The structure was identified by the following data. at 40° C. for additional 2 hours the resulting mixture was then concentrated to 150 ml The mixture was extracted with ethyl acetate (200 ml) the aqueous layer was further extracted with ethyl acetate (50 ml×2) The combined organic layers were washed with water (100 ml) and with brine (100 ml) dried over anhydrous magnesium sulfate The resulting solution was concentrated the residue was stirred at 180° C. for 2.5 hours Ether (30 ml) was added to the reaction mixture The resulting mixture was then treated with diazomethane After removing off ether the residue was further distilled under reduced pressure

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

Procedure: To a solution of ethyl 2-ethoxycarbonyl-3,3-dimethylhexanoate (24.5 g, 100 mmol) in ethanol (150 ml), was added aqueous sodium hydroxide solution (1N, 180 ml, 180 mmol) and the mixture was stirred at room temperature for 24 hours and then at 40° C. for additional 2 hours. Aqueous hydrogen chloride (3N, 60 ml, 180 mmol) was added to the reaction mixture and the resulting mixture was then concentrated to 150 ml. The mixture was extracted with ethyl acetate (200 ml) and the aqueous layer was further extracted with ethyl acetate (50 ml×2). The combined organic layers were washed with water (100 ml) and with brine (100 ml), and dried over anhydrous magnesium sulfate. The resulting solution was concentrated and the residue was stirred at 180° C. for 2.5 hours. Ether (30 ml) was added to the reaction mixture. The resulting mixture was then treated with diazomethane. After removing off ether, the residue was further distilled under reduced pressure to give oily product, ethyl 3,3-dimethylhexanoate (11.07 g, 64.4 mmol), 64.4%, b.p.: 87°-94° C./22 mmHg). The structure was identified by the following data. at 40° C. for additional 2 hours the resulting mixture was then concentrated to 150 ml The mixture was extracted with ethyl acetate (200 ml) the aqueous layer was further extracted with ethyl acetate (50 ml×2) The combined organic layers were washed with water (100 ml) and with brine (100 ml) dried over anhydrous magnesium sulfate The resulting solution was concentrated the residue was stirred at 180° C. for 2.5 hours Ether (30 ml) was added to the reaction mixture The resulting mixture was then treated with diazomethane After removing off ether the residue was further distilled under reduced pressure

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

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

Procedure: Ethyl 3,3-dimethylhexanoate (from above) (280 g, 1.63 mol), ethyl alcohol (400 mL) and aqueous sodium hydroxide solution (98 g, 2.45 mol, in 200 mL of water) were added to a 2-L round flask equipped with a stirring bar. The solution was then heated to refluxing temperature and stirred for 24 hours. After the reaction was finished, most of the solvents were removed by evaporation. The residue was taken up in 500 mL of ice water. It was then acidified to pH=3 with HCl (10%, w. ˜500 mL). The mixture was extracted with MTBE (3×500 mL). The combined MTBE extracts were washed with brine (2×50 mL) and dried over magnesium sulfate (˜40 g). The drying reagent was filtered and the MTBE was removed to give 223 g of 3,3-dimethylhexanoic acid (yield 95.1%). 1H NMR (CDCl3/300 MHz): δ2.25(s, 2H), 1.32-1.26(m, 4H), 1.02(s, 6H), 0.90(m, 3H) ppm; 13C NMR (CDCl3/300 MHz): δ179.0, 45.8, 44.6, 33.2, 27.2, 17.5, 14.8 ppm; MS 162 (M++NH4+). equipped with a stirring bar The solution was then heated to refluxing temperature were removed by evaporation The mixture was extracted with MTBE (3×500 mL) The combined MTBE extracts were washed with brine (2×50 mL) dried over magnesium sulfate (˜40 g) The drying reagent was filtered the MTBE was removed

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dimethyl methylphosphonate (11.7 g, 102 mmol) was dissolved in anhydrous THF (200 ml) and the resulting solution was cooled to -78° C. under argon atmosphere. A solution of n-butyl lithium in hexane (1.63N, 62.3 ml, 102 mmol) was added and the mixture was stirred for 30 minutes. A solution of ethyl 3,3-dimethylhexanoate (7.00 g, 40.6 mmol) in anhydrous THF (50 ml) was added to the reaction mixture at -78° C. andthe mixture was stirred for 30 minutes and then at room temperature for further 2 hours. Acetic acid was added to neutralize the solution. Water (20 ml) was added and then the solution was concentrated. The resulting residue were partitioned between ethyl acetate (200 ml) and water (10 ml). The ethyl acetate layer was separated, washed with water (80 ml) and with brine (100 ml), dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled under reduced pressure to give oily product, dimethyl 4,4-dimethyl-2-oxoheptylphosphonate (8.11 g, 32.4 mmol, 79.8%, b.p.: 101°-104° C./0.03 mmHg). The structure was identified by the following data. was stirred for 30 minutes at room temperature for further 2 hours the solution was concentrated The resulting residue were partitioned between ethyl acetate (200 ml) and water (10 ml) The ethyl acetate layer was separated washed with water (80 ml) and with brine (100 ml) dried over anhydrous magnesium sulfate concentrated The residue was distilled under reduced pressure

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

Procedure: To a solution of ethyl 2-ethoxycarbonyl-3,3-dimethylhexanoate (24.5 g, 100 mmol) in ethanol (150 ml), was added aqueous sodium hydroxide solution (1N, 180 ml, 180 mmol) and the mixture was stirred at room temperature for 24 hours and then at 40° C. for additional 2 hours. Aqueous hydrogen chloride (3N, 60 ml, 180 mmol) was added to the reaction mixture and the resulting mixture was then concentrated to 150 ml. The mixture was extracted with ethyl acetate (200 ml) and the aqueous layer was further extracted with ethyl acetate (50 ml×2). The combined organic layers were washed with water (100 ml) and with brine (100 ml), and dried over anhydrous magnesium sulfate. The resulting solution was concentrated and the residue was stirred at 180° C. for 2.5 hours. Ether (30 ml) was added to the reaction mixture. The resulting mixture was then treated with diazomethane. After removing off ether, the residue was further distilled under reduced pressure to give oily product, ethyl 3,3-dimethylhexanoate (11.07 g, 64.4 mmol), 64.4%, b.p.: 87°-94° C./22 mmHg). The structure was identified by the following data. at 40° C. for additional 2 hours the resulting mixture was then concentrated to 150 ml The mixture was extracted with ethyl acetate (200 ml) the aqueous layer was further extracted with ethyl acetate (50 ml×2) The combined organic layers were washed with water (100 ml) and with brine (100 ml) dried over anhydrous magnesium sulfate The resulting solution was concentrated the residue was stirred at 180° C. for 2.5 hours Ether (30 ml) was added to the reaction mixture The resulting mixture was then treated with diazomethane After removing off ether the residue was further distilled under reduced pressure