cyclooctylmethanol

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

Procedure: A solution of 8 millimols of cobalt 2-ethylhexoate and 20 millimols of triethylphosphate in 200 ml. of benzene was treated in an autoclave with 1:1 H2 :CO mixture for one hour at 170° C. and 3,700-114 3,750 psig. The autoclave was cooled and vented, and 250 g. of 1,5-cyclooctadiene was added. This mixture was treated with 1:1 H2 :CO at 145°-185° C. and 1,800-3,000 psig. for 3 hours. Distillation of the reactor effluent gave 203 g. of hydroformylation products boiling at 36°-75° C. at 5 mm. Hg pressure and 79 g. of residue. Reduction of a portion of the distilled oxygenated products over a nickel-based catalyst with hydrogen at elevated temperatures and pressures gave a 90% yield of hydroxymethylcyclooctane. The autoclave was cooled This mixture was treated with 1:1 H2 at 145°-185° C. for 3 hours Distillation of the reactor effluent gave 203 g Reduction of a portion of the distilled oxygenated products over a nickel-

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

Procedure: A solution of 8 millimols of cobalt 2-ethylhexoate and 20 millimols of triethylphosphate in 200 ml. of benzene was treated in an autoclave with 1:1 H2 :CO mixture for one hour at 170° C. and 3,700-114 3,750 psig. The autoclave was cooled and vented, and 250 g. of 1,5-cyclooctadiene was added. This mixture was treated with 1:1 H2 :CO at 145°-185° C. and 1,800-3,000 psig. for 3 hours. Distillation of the reactor effluent gave 203 g. of hydroformylation products boiling at 36°-75° C. at 5 mm. Hg pressure and 79 g. of residue. Reduction of a portion of the distilled oxygenated products over a nickel-based catalyst with hydrogen at elevated temperatures and pressures gave a 90% yield of hydroxymethylcyclooctane. The autoclave was cooled This mixture was treated with 1:1 H2 at 145°-185° C. for 3 hours Distillation of the reactor effluent gave 203 g Reduction of a portion of the distilled oxygenated products over a nickel-

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

Procedure: Mitsunobu reaction of phenol 58 with cyclooctane Methanol gave 2-(3-(3-(cyclooctylmethoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.920 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.86 (m, 2H), 7.68-7.73 (m, 2H), 7.10-7.13 (m, 1H), 6.72-6.79 (m, 2H), 6.64-6.68 (m, 1H), 3.65 (d, J=6.4 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 1.98-2.06 (m, 4H), 1.65-1.78 (m, 7H), 1.56-1.64 (m, 5H), 1.30-1.40 (m, 3H).

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

Procedure: Mitsunobu reaction of phenol 58 with cyclooctane Methanol gave 2-(3-(3-(cyclooctylmethoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.920 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.86 (m, 2H), 7.68-7.73 (m, 2H), 7.10-7.13 (m, 1H), 6.72-6.79 (m, 2H), 6.64-6.68 (m, 1H), 3.65 (d, J=6.4 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 1.98-2.06 (m, 4H), 1.65-1.78 (m, 7H), 1.56-1.64 (m, 5H), 1.30-1.40 (m, 3H).

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

Procedure: Mitsunobu reaction of phenol 58 with cyclooctane methanol gave 2-(3-(3-(cyclooctylmethoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.920 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.86 (m, 2H), 7.68-7.73 (m, 2H), 7.10-7.13 (m, 1H), 6.72-6.79 (m, 2H), 6.64-6.68 (m, 1H), 3.65 (d, J=6.4 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 1.98-2.06 (m, 4H), 1.65-1.78 (m, 7H), 1.56-1.64 (m, 5H), 1.30-1.40 (m, 3H).

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

Procedure: Mitsunobu reaction of phenol 58 with cyclooctane methanol gave 2-(3-(3-(cyclooctylmethoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.920 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.86 (m, 2H), 7.68-7.73 (m, 2H), 7.10-7.13 (m, 1H), 6.72-6.79 (m, 2H), 6.64-6.68 (m, 1H), 3.65 (d, J=6.4 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 1.98-2.06 (m, 4H), 1.65-1.78 (m, 7H), 1.56-1.64 (m, 5H), 1.30-1.40 (m, 3H).

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

Procedure: Mitsunobu reaction of phenol 58 with cyclooctane methanol gave 2-(3-(3-(cyclooctylmethoxy)phenyl)propyl)isoindoline-1,3-dione as yellow oil. Yield (0.920 g, 65%): 1H NMR (400 MHz, CDCl3) δ 7.80-7.86 (m, 2H), 7.68-7.73 (m, 2H), 7.10-7.13 (m, 1H), 6.72-6.79 (m, 2H), 6.64-6.68 (m, 1H), 3.65 (d, J=6.4 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 1.98-2.06 (m, 4H), 1.65-1.78 (m, 7H), 1.56-1.64 (m, 5H), 1.30-1.40 (m, 3H).

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

Procedure: 1-Ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (150 mg), 1-hydroxybenzotriazole (110 mg) and diisopropylethylamine (0.23 ml) were added to a DMF (5 ml) solution containing the resulting compound (190 mg) and 4-(cyclooctylmethoxy)benzoic acid (176 mg) prepared from cyclooctylmethanol with reference to Reference Example 70, followed by stirring overnight at room temperature. The reaction solution was diluted with EtOAc, the organic layer was washed with aqueous saturated sodium hydrogencarbonate solution, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOAc/hexane to obtain 3-pyridyl 4-[4-(cyclooctylmethoxy)benzoyl]-1-piperazinecarboxylate (240 mg). the organic layer was washed with aqueous saturated sodium hydrogencarbonate solution dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was recrystallized from EtOAc/hexane

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

Procedure: 1-Ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (150 mg), 1-hydroxybenzotriazole (110 mg) and diisopropylethylamine (0.23 ml) were added to a DMF (5 ml) solution containing the resulting compound (190 mg) and 4-(cyclooctylmethoxy)benzoic acid (176 mg) prepared from cyclooctylmethanol with reference to Reference Example 70, followed by stirring overnight at room temperature. The reaction solution was diluted with EtOAc, the organic layer was washed with aqueous saturated sodium hydrogencarbonate solution, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOAc/hexane to obtain 3-pyridyl 4-[4-(cyclooctylmethoxy)benzoyl]-1-piperazinecarboxylate (240 mg). the organic layer was washed with aqueous saturated sodium hydrogencarbonate solution dried over anhydrous sodium sulfate The solvent was evaporated under reduced pressure the residue was recrystallized from EtOAc/hexane

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

Procedure: Cyclooctylmethanol (8.16 g) was dissolved in 47% HBr-solution (70 ml) and refluxed for 1 hour at 130° C. The reaction mixture was poured onto icewater (500 ml) and saturated sodium hydrogencarbonate solution (500 ml) was added. The aqueous solution was extracted with dichloromethane. The combined organic phases were washed with water, brine and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel in toluene as eluent. The fractions containing cyclo-octylmethyl bromide were pooled and evaporated. Yield: 9.85 g. TLC: Rf=0.95, silica gel, toluene was added The aqueous solution was extracted with dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel in toluene as eluent The fractions containing cyclo-octylmethyl bromide evaporated

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

Procedure: Cyclooctylmethanol (8.16 g) was dissolved in 47% HBr-solution (70 ml) and refluxed for 1 hour at 130° C. The reaction mixture was poured onto icewater (500 ml) and saturated sodium hydrogencarbonate solution (500 ml) was added. The aqueous solution was extracted with dichloromethane. The combined organic phases were washed with water, brine and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel in toluene as eluent. The fractions containing cyclo-octylmethyl bromide were pooled and evaporated. Yield: 9.85 g. TLC: Rf=0.95, silica gel, toluene was added The aqueous solution was extracted with dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel in toluene as eluent The fractions containing cyclo-octylmethyl bromide evaporated

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

Procedure: Cyclooctylmethanol (8.16 g) was dissolved in 47% HBr-solution (70 ml) and refluxed for 1 hour at 130° C. The reaction mixture was poured onto icewater (500 ml) and saturated sodium hydrogencarbonate solution (500 ml) was added. The aqueous solution was extracted with dichloromethane. The combined organic phases were washed with water, brine and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel in toluene as eluent. The fractions containing cyclo-octylmethyl bromide were pooled and evaporated. Yield: 9.85 g. TLC: Rf=0.95, silica gel, toluene was added The aqueous solution was extracted with dichloromethane The combined organic phases were washed with water, brine dried over sodium sulfate filtered concentrated in vacuo The residue was chromatographed on silica gel in toluene as eluent The fractions containing cyclo-octylmethyl bromide evaporated