2-(4,4-dimethylcyclohexyl)ethanol

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: To a solution of 2-(4,4-dimethylcyclohexyl)-1-ethanol (Preparation 15, 1.45 g, 9 mmol) and 4-bromobenzenesulfonyl chloride (2.53 g, 10 mmol) in dichloromethane (30 ml) was added triethylamine (1.9 ml, 13.5 mmol), and the reaction mixture was allowed to stir at room temperature for 24 h. After a further addition of 4-bromobenzenesulfonyl chloride (2.53 g, 10 mmol) and triethylamine (1.9 ml, 13.5 mmol), the reaction mixture was heated under reflux for 1 h. After allowing the reaction mixture to cool to room temperature, the mixture was treated with 2N aqueous hydrochloric acid (100 ml) and the phases were separated. The organic extract was dried (MgSO4), filtered and concentrated in vacuo to afford the crude product. The residue was purified by silica (80 g) column chromatography eluting with diethyl ether:hexane (1:20) to give the title compound as a colourless oil (450 mg, 13%). the reaction mixture was heated under reflux for 1 h to cool to room temperature the phases were separated The organic extract was dried (MgSO4) filtered concentrated in vacuo to afford the crude product The residue was purified by silica (80 g) column chromatography eluting with diethyl ether:hexane (1:20)

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

Procedure: To a solution of ethyl 2-(4,4-dimethylcyclohexyl)acetate (Preparation 14, 2.0 g, 10 mmol) in tetrahydrofuran (20 ml) under an atmosphere of nitrogen at 0° C. was added lithium aluminium hydride (1.0M solution in tetrahydrofuran, 11 ml, 11 mmol) and the reaction mixture was allowed to warm to room temperature overnight. The mixture was poured onto ice (300 g), acidified to pH 1 with 1N aqueous hydrochloric acid and extracted with dichloromethane (200 ml). The organic extract was dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a pale yellow oil (1.45 g, 93%). The mixture was poured onto ice (300 g) extracted with dichloromethane (200 ml) The organic extract was dried (MgSO4) filtered concentrated in vacuo

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4,4-dimethylcyclohexyl)ethanol (WO99/59971) (2 g, 12.8 mmol), concentrated sulphuric acid (750 μl) and 48% hydrobromic acid (3 ml) was stirred at 90° C. for 7 hours. The cooled mixture was then carefully quenched by the addition of water (25 ml), and the mixture was extracted with dichloromethane (3×30 ml). The combined organic extracts were washed with 2M sodium carbonate solution and brine (30ml), then dried (MgSO4) and concentrated under reduced pressure. The residual black gum was purified by distillation to afford the title compound, 330 mg. 1H-NMR (CDCl3, 400 MHz) δ: 0.82 (2×s, 6H), 1.02-1.20 (m, 4H), 1.35 (m, 3H), 1.50 (m, 2H), 1.78 (m, 2H), 3.40 (t, 2H). The cooled mixture was then carefully quenched by the addition of water (25 ml) the mixture was extracted with dichloromethane (3×30 ml) The combined organic extracts were washed with 2M sodium carbonate solution and brine (30ml) dried (MgSO4) concentrated under reduced pressure The residual black gum was purified by distillation

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

Procedure: To a solution of 2-(4,4-dimethylcyclohexyl)-1-ethanol (Preparation 15, 1.45 g, 9 mmol) and 4-bromobenzenesulfonyl chloride (2.53 g, 10 mmol) in dichloromethane (30 ml) was added triethylamine (1.9 ml, 13.5 mmol), and the reaction mixture was allowed to stir at room temperature for 24 h. After a further addition of 4-bromobenzenesulfonyl chloride (2.53 g, 10 mmol) and triethylamine (1.9 ml, 13.5 mmol), the reaction mixture was heated under reflux for 1 h. After allowing the reaction mixture to cool to room temperature, the mixture was treated with 2N aqueous hydrochloric acid (100 ml) and the phases were separated. The organic extract was dried (MgSO4), filtered and concentrated in vacuo to afford the crude product. The residue was purified by silica (80 g) column chromatography eluting with diethyl ether:hexane (1:20) to give the title compound as a colourless oil (450 mg, 13%). the reaction mixture was heated under reflux for 1 h to cool to room temperature the phases were separated The organic extract was dried (MgSO4) filtered concentrated in vacuo to afford the crude product The residue was purified by silica (80 g) column chromatography eluting with diethyl ether:hexane (1:20)

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

Procedure: To a solution of ethyl 2-(4,4-dimethylcyclohexyl)acetate (Preparation 14, 2.0 g, 10 mmol) in tetrahydrofuran (20 ml) under an atmosphere of nitrogen at 0° C. was added lithium aluminium hydride (1.0M solution in tetrahydrofuran, 11 ml, 11 mmol) and the reaction mixture was allowed to warm to room temperature overnight. The mixture was poured onto ice (300 g), acidified to pH 1 with 1N aqueous hydrochloric acid and extracted with dichloromethane (200 ml). The organic extract was dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a pale yellow oil (1.45 g, 93%). The mixture was poured onto ice (300 g) extracted with dichloromethane (200 ml) The organic extract was dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4,4-dimethylcyclohexyl)ethanol (WO99/59971) (2 g, 12.8 mmol), concentrated sulphuric acid (750 μl) and 48% hydrobromic acid (3 ml) was stirred at 90° C. for 7 hours. The cooled mixture was then carefully quenched by the addition of water (25 ml), and the mixture was extracted with dichloromethane (3×30 ml). The combined organic extracts were washed with 2M sodium carbonate solution and brine (30 ml), then dried (MgSO4) and concentrated under reduced pressure. The residual black gum was purified by distillation to afford the title compound, 330 mg. 1H-NMR (CDCl3, 400 MHz) δ: 0.82 (2×s, 6H), 1.02-1.20 (m, 4H), 1.35 (m, 3H), 1.50 (m, 2H), 1.78 (m, 2H), 3.40 (t, 2H). The cooled mixture was then carefully quenched by the addition of water (25 ml) the mixture was extracted with dichloromethane (3×30 ml) The combined organic extracts were washed with 2M sodium carbonate solution and brine (30 ml) dried (MgSO4) concentrated under reduced pressure The residual black gum was purified by distillation

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4,4-dimethylcyclohexyl)ethanol (WO99/59971) (2 g, 12.8 mmol), concentrated sulphuric acid (750 μl) and 48% hydrobromic acid (3 ml) was stirred at 90° C. for 7 hours. The cooled mixture was then carefully quenched by the addition of water (25 ml), and the mixture was extracted with dichloromethane (3×30 ml). The combined organic extracts were washed with 2M sodium carbonate solution and brine (30 ml), then dried (MgSO4) and concentrated under reduced pressure. The residual black gum was purified by distillation to afford the title compound, 330 mg. 1H-NMR (CDCl3, 400 MHz) δ: 0.82 (2×s, 6H), 1.02-1.20 (m, 4H), 1.35 (m, 3H), 1.50 (m, 2H), 1.78 (m, 2H), 3.40 (t, 2H). The cooled mixture was then carefully quenched by the addition of water (25 ml) the mixture was extracted with dichloromethane (3×30 ml) The combined organic extracts were washed with 2M sodium carbonate solution and brine (30 ml) dried (MgSO4) concentrated under reduced pressure The residual black gum was purified by distillation

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, to a mixture of 2-(4,4-dimethylcyclohexyl)ethanol (25.3 g) and DCM (200 mL) were added DMSO (50 mL) and TEA (100 mL), and a sulfur trioxide-pyridine complex (77.7 g) was added in small divided portions while maintaining the inner temperature to 10° C. or lower under ice-cooling. After stirring at room temperature for 2 hours, to the reaction mixture was added ice water, followed by concentration under reduced pressure and then extraction with chloroform. The organic layer was washed sequentially with 1 M hydrochloric acid and brine. To the organic layer was added MgSO4, followed by stirring. Then, the mixture was filtered and concentrated under reduced pressure to obtain (4,4-dimethylcyclohexyl)acetaldehyde (27.3 g). a sulfur trioxide-pyridine complex (77.7 g) was added lower under ice-cooling followed by concentration under reduced pressure extraction with chloroform The organic layer was washed sequentially with 1 M hydrochloric acid and brine To the organic layer was added MgSO4 by stirring Then, the mixture was filtered concentrated under reduced pressure