ethyl 9-bromo-2,2-dimethylnonanoate

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: Ethyl 2,2-dimethyl-9-bromononanoate (2.0 g, 0.007 mol) was treated with 4-chlorobenzenesulphonamide (3.44 g, 0.018 mol) and potassium carbonate (6.2 g, 0.045 mol) by the method described in Example 5(ii) to give the title compound (1.5 g) as an oil.

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

Procedure: A mixture of 2,4,5-triphenylimidazole (4.13 g), ethyl 9-bromo-2,2-dimethylnonanoate (10.95 g), potassium carbonate (10 g) and 2-butanone was stirred at reflux for 48 hours. The mixture was filtered, solvent removed under reduced pressure and the residue was chromatographed on silica gel eluted with chloroform to give a clear oil which was dissolved in dimethyl sulphoxide (30 ml) and treated with potassium hydroxide (3 g). The mixture was stirred at 40° C. for 24 hours when the solvent was removed under reduced pressure. Water (50 ml) was added, the pH of the solution was adjusted to 4 and the aqueous was extracted with chloroform (3×50 ml). The chloroform extracts were dried over magnesium sulphate, filtered and the solvent removed to give a solid which was recrystallised from acetonitrile to give 9-(1,2,4-tri-phenylimidazolyl)-2,2-dimethylnonanoic acid as a white crystalline solid, m.p. 119°-120° C.; Found: C, 79.85; H, 7.64; N, 6.23% (C32H36N2O2); Requires: C, 79.96; H, 5.54; N, 5.82% at reflux for 48 hours The mixture was filtered solvent removed under reduced pressure the residue was chromatographed on silica gel eluted with chloroform to give a clear oil which The mixture was stirred at 40° C. for 24 hours when the solvent was removed under reduced pressure Water (50 ml) was added the aqueous was extracted with chloroform (3×50 ml) The chloroform extracts were dried over magnesium sulphate filtered the solvent removed to give a solid which was recrystallised from acetonitrile

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

Procedure: A mixture of 2,4,5-triphenylimidazole (4.13 g), ethyl 9-bromo-2,2-dimethylnonanoate (10.95 g), potassium carbonate (10 g) and 2-butanone was stirred at reflux for 48 hours. The mixture was filtered, solvent removed under reduced pressure and the residue was chromatographed on silica gel eluted with chloroform to give a clear oil which was dissolved in dimethyl sulphoxide (30 ml) and treated with potassium hydroxide (3 g). The mixture was stirred at 40° C. for 24 hours when the solvent was removed under reduced pressure. Water (50 ml) was added, the pH of the solution was adjusted to 4 and the aqueous was extracted with chloroform (3×50 ml). The chloroform extracts were dried over magnesium sulphate, filtered and the solvent removed to give a solid which was recrystallised from acetonitrile to give 9-(1,2,4-tri-phenylimidazolyl)-2,2-dimethylnonanoic acid as a white crystalline solid, m.p. 119°-120° C.; Found: C, 79.85; H, 7.64; N, 6.23% (C32H36N2O2); Requires: C, 79.96; H, 5.54; N, 5.82% at reflux for 48 hours The mixture was filtered solvent removed under reduced pressure the residue was chromatographed on silica gel eluted with chloroform to give a clear oil which The mixture was stirred at 40° C. for 24 hours when the solvent was removed under reduced pressure Water (50 ml) was added the aqueous was extracted with chloroform (3×50 ml) The chloroform extracts were dried over magnesium sulphate filtered the solvent removed to give a solid which was recrystallised from acetonitrile

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

Procedure: Under N2 atmosphere at 0° C., LDA (2 M solution in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 3.0 g, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) over 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl solution (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1) to give 205j (3.42 g, 45%) as a colorless liquid. 1H NMR (CDCl3): δ (ppm): 4.11 (q, J=7.2, 2 H), 3.40 (t, J=6.9, 2 H), 1.85 (quintet, J=6.9, 2 H), 1.52-1.47 (m, 2 H), 1.45-1.36 (m, 2 H), 1.35-1.20 (m, 6 H), 1.24 (t, J=7.2, 3 H), 1.15 (s, 6 H). 13C-NMR (CDCl3): δ (ppm): 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS: Calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1)

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

Procedure: Under a N2 atmosphere at 0° C., LDA (2 M in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) in 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) and dried. The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice to give 103g (3.42 g, 45%) as a colorless liquid. 1H NMR δ 4.11 (q, J=7.2 Hz, 2H), 3.40 (t, J=6.9 Hz, 2H), 1.85 (quintet, J=6.9 Hz, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2 Hz, 3H), 1.15 (s, 6H). 13C NMR: δ 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) dried The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice

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

Procedure: Under N2 atmosphere at 0° C., LDA (2 M solution in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 3.0 g, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) over 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl solution (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue (12.4 g) was purified twice by column chromatography (heptane: ethyl acetate=40:1) to give 205j (3.42 g, 45%) as a colorless liquid. 1H NMR (CDCl3): δ (ppm): 4.11 (q, J=7.2, 2H), 3.40 (t, J=6.9, 2H), 1.85 (quintet, J=6.9, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2, 3H), 1.15 (s, 6H). 13C-NMR (CDCl3): δ (ppm): 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS: Calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue (12.4 g) was purified twice by column chromatography (heptane: ethyl acetate=40:1)

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

Procedure: Under a N2 atmosphere at 0° C., LDA (2 M in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) in 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) and dried. The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice to give 103g (3.42 g, 45%) as a colorless liquid. 1H NMR: δ 4.11 (q, J=7.2 Hz, 2H), 3.40 (t, J=6.9 Hz, 2H), 1.85 (quintet, J=6.9 Hz, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2 Hz, 3H), 1.15 (s, 6H). 13C NMR: δ 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) dried The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice

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

Procedure: Under a N2 atmosphere at 0° C., LDA (2 M in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) in 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) and dried. The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice to give 103g (3.42 g, 45%) as a colorless liquid. 1H NMR: δ 4.11 (q, J=7.2 Hz, 2H), 3.40 (t, J=6.9 Hz, 2H), 1.85 (quintet, J=6.9 Hz, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2 Hz, 3H), 1.15 (s, 6H). 13C NMR: δ 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) dried The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice

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

Procedure: Under N2 atmosphere at 0° C., LDA (2 M solution in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 3.0 g, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) over 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl solution (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1) to give 205j (3.42 g, 45%) as a colorless liquid. 1H NMR (CDCl3): δ (ppm): 4.11 (q, J=7.2, 2 H), 3.40 (t, J=6.9, 2 H), 1.85 (quintet, J=6.9, 2 H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2, 3 H), 1.15 (s, 6H). 13C-NMR (CDCl3): δ (ppm): 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS: Calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 solution (100 mL) and brine (100 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue (12.4 g) was purified twice by column chromatography (heptane:ethyl acetate=40:1)

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

Procedure: Under a N2 atmosphere at 0° C., LDA (2 M in THF/heptane/ethylbenzene, 13.0 mL, 26.0 mmol) was added dropwise to a mixture of ethyl isobutyrate (3.5 mL, 25.9 mmol) and 1,7-dibromoheptane (9.84 g, 38.2 mmol) in dry THF (50 mL) in 1.5 h, while keeping the temperature below 5° C. After 3 h, the mixture was poured into ice-cold saturated aqueous NH4Cl (150 mL). The layers were separated and the aqueous phase was extracted with Et2O (3×100 mL). The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) and dried. The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice to give 103g (3.42 g, 45%) as a colorless liquid. 1H NMR: δ 4.11 (q, J=7.2 Hz, 2H), 3.40 (t, J=6.9 Hz, 2H), 1.85 (quintet, J=6.9 Hz, 2H), 1.52-1.47 (m, 2H), 1.45-1.36 (m, 2H), 1.35-1.20 (m, 6H), 1.24 (t, J=7.2 Hz, 3H), 1.15 (s, 6H). 13C NMR: δ 177.8, 60.0, 42.0, 40.5, 33.7, 32.7, 29.7, 28.5, 28.0, 25.0 (2×), 24.7, 14.1. HRMS calcd for C13H25BrO2 (M+): 292.1038, found: 292.1034. the temperature below 5° C The layers were separated the aqueous phase was extracted with Et2O (3×100 mL) The combined organic layers were washed with aqueous HCl (1 M, 100 mL), saturated aqueous NaHCO3 (100 mL) and brine (100 mL) dried The remaining residue was purified by column chromatography (heptane:EtOAc=40:1) twice