propan-2-yl cyclohexanecarboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropylamine (1.90 g, 18.75 mmol) in THF (9 mL) 1.6 M n-BuLi in hexane (10.6 mL, 16.9 mmol) was added with stirring over 20 min at −65° C. The suspension was warmed up to −40° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (2.393 g, 14.1 mmol) in THF (20 mL) at −65° C. The resulting solution was stirred 0.5 h at −65° C., then 1-bromo-2-ethylbutane (3.249 g, 19.68 mmol) in THF (10 mL) was added at −65° C. over 15 min. The solution was stirred 1.5 h at −65° C. and then overnight without a cooling bath while slowly warming up to room temperature. At 5° C. ice-water (15 mL) was added, followed by 2N HCl (30 mL). The organic phase was diluted with ethyl acetate and washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (3.5 g) was distilled at 55° C. (0.01 mbar) to give 2.9 g (81%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as a colorless oil, purity 93% (GC area) (cyclohexanecarboxylic acid diisopropylamide as impurity: 0.9% in dist. product and 0.7% in crude product). The suspension was warmed up to −40° C. The resulting solution was stirred 0.5 h at −65° C. The solution was stirred 1.5 h at −65° C. overnight without a cooling bath while slowly warming up to room temperature washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (3.5 g) was distilled at 55° C. (0.01 mbar)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of dicyclohexylamine (4.263 g, 23.5 mmol) in THF (10 mL) 1.6 M n-BuLi in hexane (13.23 mL, 21.15 mmol) was added with stirring over 20 min at temperature between −20° C. and −15° C. This orange suspension was stirred 10 min at −20° C. and then warmed up to 0° C. To this orange suspension a solution of cyclohexanecarboxylic acid isopropyl ester (3.0 g, 17.63 mmol) in THF (22 mL) was added over 15 min at 0° C. The resulting solution was stirred 30 min at 0° C., then 1-bromo-2-ethylbutane (4.073 g, 24.7 mmol) in THF (11 mL) was added at the same temperature over 15 min. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature. At 5° C. cold water (20 mL) was added, followed by 2N HCl (50 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (4.7 g) was distilled at 50° C. (0.01 mbar) to give 3.95 g (88%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 97% (GC area). This orange suspension was stirred 10 min at −20° C. The resulting solution was stirred 30 min at 0° C. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature The white suspension was filtered the filter cake was washed with water and ethyl acetate The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (4.7 g) was distilled at 50° C. (0.01 mbar)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of dicyclohexylamine (4.263 g, 23.5 mmol) in THF (10 mL) 1.6 M n-BuLi in hexane (13.23 mL, 21.15 mmol) was added with stirring over 20 min at temperature between −20° C. and −15° C. This orange suspension was stirred 10 min at −20° C. and then warmed up to 0° C. To this orange suspension a solution of cyclohexanecarboxylic acid isopropyl ester (3.0 g, 17.63 mmol) in THF (22 mL) was added over 15 min at 0° C. The resulting solution was stirred 30 min at 0° C., then 1-bromo-2-ethylbutane (4.073 g, 24.7 mmol) in THF (11 mL) was added at the same temperature over 15 min. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature. At 5° C. cold water (20 mL) was added, followed by 2N HCl (50 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (4.7 g) was distilled at 50° C. (0.01 mbar) to give 3.95 g (88%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 97% (GC area). This orange suspension was stirred 10 min at −20° C. The resulting solution was stirred 30 min at 0° C. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature The white suspension was filtered the filter cake was washed with water and ethyl acetate The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (4.7 g) was distilled at 50° C. (0.01 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of dicyclohexylamine (14.24 g, 78.5 mmol) in THF (35 mL) 1.6 M n-BuLi in hexane (44.2 mL, 70.7 mmol) was added with stirring over 50 min at temperature between −20° C. and −15° C. The resulting orange suspension was stirred 10 min at −20° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (10.0 g, 58.75 mmol) in THF (75 mL) at 0-2° C. To the resulting solution 1-bromo-2-ethylbutane (13.58 g, 82.25 mmol) in THF (37.5 mL) was added at 0° C. over 15 min. The solution was stirred overnight at 0° C. and for an other 3 h at room temperature. At 5° C. ice-water (25 mL) was added, followed by 2N HCl (60 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (15.5 g) was distilled at 60° C. (0.05 mbar) to give 12.7 g (85%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 99.2% (GC area). 1H-NMR (CDCl3, 400 MHz): ppm 0.80 (t, 6H), 1.15-1.39 (m, 11H), 1.23 (d, 6H), 1.40 (d, 2H), 1.51-1.59 (m, 2H), 2.02-2.12 (m, 2H). 4.95-5.05 (m, 1H). The resulting orange suspension was stirred 10 min at −20° C. The solution was stirred overnight at 0° C. and for an other 3 h at room temperature The white suspension was filtered the filter cake was washed with water and ethyl acetate The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (15.5 g) was distilled at 60° C. (0.05 mbar)

反応条件: temp:71.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanecarboxylic acid (22.0 g, 172 mmol) in isopropanol (66 mL) and cyclohexane (44 mL) p-TsOH (653 mg, 3.43 mmol) was added. The mixture was heated with stirring to 70-73° C. and solvent was slowly distilled off whereas the volume was kept relatively constant by addition of fresh solvent mixture. After 6 h, a second portion of p-TsOH (653 mg, 3.43 mmol) was added and the reaction mixture was stirred at 71° C. overnight (without distilling off solvent). After a total of 24 h, the cooled reaction mixture was concentrated to ¼ volume. Ice and saturated aq. NaHCO3 were added and the mixture was extracted twice with TBME. The organic phases were washed to neutral with diluted aq. NaCl solution, combined, dried over sodium sulfate and concentrated. The crude product (28.5 g) was distilled at 40° C. (0.2-0.16 mbar) to afford 27.75 g (93%) cyclohexanecarboxylic acid isopropyl ester as a colorless liquid, GC purity 98% (area). 1H-NMR (CDCl3, 400 MHz): ppm 1.21 (d, 6H), 1.17-1.34 (m, 3H), 1.35-1.49 (m, 2H), 1.55-1.80 (m, 3H), 1.82-1.92 (m, 2H), 2.20-2.29 (m, 1H), 4.94-5.04 (m, 1H). The mixture was heated solvent was slowly distilled off whereas the volume was kept relatively constant by addition of fresh solvent mixture the reaction mixture was stirred at 71° C. overnight (without distilling off solvent) After a total of 24 h, the cooled reaction mixture was concentrated Ice and saturated aq. NaHCO3 were added the mixture was extracted twice with TBME The organic phases were washed to neutral with diluted aq. NaCl solution dried over sodium sulfate concentrated The crude product (28.5 g) was distilled at 40° C. (0.2-0.16 mbar)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of diisopropylamine (1.90 g, 18.75 mmol) in THF (9 mL) 1.6 M n-BuLi in hexane (10.6 mL, 16.9 mmol) was added with stirring over 20 min at −65° C. The suspension was warmed up to −40° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (2.393 g, 14.1 mmol) in THF (20 mL) at −65° C. The resulting solution was stirred 0.5 h at −65° C., then 1-bromo-2-ethylbutane (3.249 g, 19.68 mmol) in THF (10 mL) was added at −65° C. over 15 min. The solution was stirred 1.5 h at −65° C. and then overnight without a cooling bath while slowly warming up to room temperature. At 5° C. ice-water (15 mL) was added, followed by 2N HCl (30 mL). The organic phase was diluted with ethyl acetate and washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (3.5 g) was distilled at 55° C. (0.01 mbar) to give 2.9 g (81%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as a colorless oil, purity 93% (GC area) (cyclohexanecarboxylic acid diisopropylamide as impurity: 0.9% in dist. product and 0.7% in crude product). The suspension was warmed up to −40° C. The resulting solution was stirred 0.5 h at −65° C. The solution was stirred 1.5 h at −65° C. overnight without a cooling bath while slowly warming up to room temperature washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (3.5 g) was distilled at 55° C. (0.01 mbar)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of dicyclohexylamine (4.263 g, 23.5 mmol) in THF (10 mL) 1.6 M n-BuLi in hexane (13.23 mL, 21.15 mmol) was added with stirring over 20 min at temperature between −20° C. and −15° C. This orange suspension was stirred 10 min at −20° C. and then warmed up to 0° C. To this orange suspension a solution of cyclohexanecarboxylic acid isopropyl ester (3.0 g, 17.63 mmol) in THF (22 mL) was added over 15 min at 0° C. The resulting solution was stirred 30 min at 0° C., then 1-bromo-2-ethylbutane (4.073 g, 24.7 mmol) in THF (11 mL) was added at the same temperature over 15 min. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature. At 5° C. cold water (20 mL) was added, followed by 2N HCl (50 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (4.7 g) was distilled at 50° C. (0.01 mbar) to give 3.95 g (88%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 97% (GC area). This orange suspension was stirred 10 min at −20° C. The resulting solution was stirred 30 min at 0° C. Stirring at 0° C. was continued overnight and for an additional 2 h at room temperature The white suspension was filtered the filter cake was washed with water and ethyl acetate The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (4.7 g) was distilled at 50° C. (0.01 mbar)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of dicyclohexylamine (14.24 g, 78.5 mmol) in THF (35 mL) 1.6 M n-BuLi in hexane (44.2 mL, 70.7 mmol) was added with stirring over 50 min at temperature between −20° C. and −15° C. The resulting orange suspension was stirred 10 min at −20° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (10.0 g, 58.75 mmol) in THF (75 mL) at 0-2° C. To the resulting solution 1-bromo-2-ethylbutane (13.58 g, 82.25 mmol) in THF (37.5 mL) was added at 0° C. over 15 min. The solution was stirred overnight at 0° C. and for an other 3 h at room temperature. At 5° C. ice-water (25 mL) was added, followed by 2N HCl (60 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (15.5 g) was distilled at 60° C. (0.05 mbar) to give 12.7 g (85%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 99.2% (GC area). 1H-NMR (CDCl3, 400 MHz): ppm 0.80 (t, 6H), 1.15-1.39 (m, 11H), 1.23 (d, 6H), 1.40 (d, 2H), 1.51-1.59 (m, 2H), 2.02-2.12 (m, 2H). 4.95-5.05 (m, 1H). The resulting orange suspension was stirred 10 min at −20° C. The solution was stirred overnight at 0° C. and for an other 3 h at room temperature The white suspension was filtered the filter cake was washed with water and ethyl acetate The organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl The aqueous phases were extracted with ethyl acetate dried over sodium sulfate concentrated The crude product (15.5 g) was distilled at 60° C. (0.05 mbar)

反応条件: temp:71.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of cyclohexanecarboxylic acid (22.0 g, 172 mmol) in isopropanol (66 mL) and cyclohexane (44 mL) p-TsOH (653 mg, 3.43 mmol) was added. The mixture was heated with stirring to 70-73° C. and solvent was slowly distilled off whereas the volume was kept relatively constant by addition of fresh solvent mixture. After 6 h, a second portion of p-TsOH (653 mg, 3.43 mmol) was added and the reaction mixture was stirred at 71° C. overnight (without distilling off solvent). After a total of 24 h, the cooled reaction mixture was concentrated to ¼ volume. Ice and saturated aq. NaHCO3 were added and the mixture was extracted twice with TBME. The organic phases were washed to neutral with diluted aq. NaCl solution, combined, dried over sodium sulfate and concentrated. The crude product (28.5 g) was distilled at 40° C. (0.2-0.16 mbar) to afford 27.75 g (93%) cyclohexanecarboxylic acid isopropyl ester as a colorless liquid, GC purity 98% (area). 1H-NMR (CDCl3, 400 MHz): ppm 1.21 (d, 6H), 1.17-1.34 (m, 3H), 1.35-1.49 (m, 2H), 1.55-1.80 (m, 3H), 1.82-1.92 (m, 2H), 2.20-2.29 (m, 1H), 4.94-5.04 (m, 1H). The mixture was heated solvent was slowly distilled off whereas the volume was kept relatively constant by addition of fresh solvent mixture the reaction mixture was stirred at 71° C. overnight (without distilling off solvent) After a total of 24 h, the cooled reaction mixture was concentrated Ice and saturated aq. NaHCO3 were added the mixture was extracted twice with TBME The organic phases were washed to neutral with diluted aq. NaCl solution dried over sodium sulfate concentrated The crude product (28.5 g) was distilled at 40° C. (0.2-0.16 mbar)