4-ethylhexanoic acid

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(2-Ethyl-butyl)-malonic acid (3.55 g, 18.8 mmol) was heated at 195° C. for 2 h. After this time, the solution was cooled to 25° C. and diluted with a 90/10 methylene chloride/methanol solution. The organics were then washed with a saturated aqueous sodium chloride solution, concentrated in vacuo and azeotroped with acetonitrile (2×50 mL) to afford 4-ethyl-hexanoic acid (1.24 mg, 45%) as yellow oil, which was used without further purification; EI+-HRMS m/e calcd for C8H16O2 [M−H]+ 143.1072, found 143.1074. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.81 (t, J=7.2 Hz, 6H) 1.02-1.35 (m, 5H) 1.32-1.59 (m, 2H) 2.16 (t, J=7.8 Hz, 2H) 11.98 (br. s., 1H). The organics were then washed with a saturated aqueous sodium chloride solution concentrated in vacuo azeotroped with acetonitrile (2×50 mL)

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

Procedure: 4-Ethylhexanoic acid (47.0 g) was dissolved in DMF (190 mL). To the solution were added piperidine (34.0 mL), HOBt.H2O (52.7 g) and WSC.HCl (66.1 g). The mixture was stirred at RT overnight. To the reaction mixture were added ethyl acetate (300 mL) and 1 N hydrochloric acid (100 mL) at ice temperature. The aqueous layer was removed and the organic layer was washed with saturated aqueous sodium bicarbonate (150 mL×2) and brine (100 mL×2), then dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (59.8 g) as a crude product. The aqueous layer was removed the organic layer was washed with saturated aqueous sodium bicarbonate (150 mL×2) and brine (100 mL×2) dried over sodium sulfate The sodium sulfate was filtered off the filtrate was concentrated in vacuo

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

Procedure: Eethyl 4-ethyl-2-hexenoate (55.3 g) was dissolved in a mixture of tetrahydrofuran (150 mL) and ethanol (150 mL). To the solution was added 5 w/w % palladium on activated carbon (5.5 g). The mixture was stirred at RT for 3.5 hr under hydrogen atmosphere (1 atm). The 5 w/w % palladium on activated carbon was filtered off using Celite. To the filtrate was added aqueous 4 N sodium hydroxide (111 mL). The mixture was stirred at RT overnight. The reaction mixture was washed with hexane. To the aqueous layer was added 4 N hydrochloric acid (113 mL). The mixture was extracted with ethyl acetate. The organic layer was washed with water/brine=1/1 (300 mL) and brine (150 mL), then dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (47.0 g) as a crude product. was filtered off To the filtrate was added aqueous 4 N sodium hydroxide (111 mL) The mixture was stirred at RT overnight The reaction mixture was washed with hexane To the aqueous layer was added 4 N hydrochloric acid (113 mL) The mixture was extracted with ethyl acetate The organic layer was washed with water/brine=1/1 (300 mL) and brine (150 mL) dried over sodium sulfate The sodium sulfate was filtered off the filtrate was concentrated in vacuo