1-(4-chlorophenyl)-3-methylbutan-2-ol

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 concentrated sulfuric acid (3.00 mL, 0.056 mol) in water (0.28 mL, 0.0156 mol) was added 1-(4-chlorophenyl)-3-methylbutan-2-ol (1.00 g, 0.00503 mol) over 30 minutes. Additional sulfuric acid was added to dissolve the solid. The mixture was stirred for 2 hours. The mixture was poured onto ice then extracted with ether. The organic phase was washed (water), dried (MgSO4), filtered, and concentrated. The residue was filtered through a plug of silica with CH2Cl2 to afford the title compound (0.568 g, 63%). to dissolve the solid The mixture was poured onto ice then extracted with ether The organic phase was washed (water) dried (MgSO4) filtered concentrated The residue was filtered through a plug of silica with CH2Cl2

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of magnesium (2.98 g, 0.123 mol) in ether (30 mL) was added iodine (0.165 g, 0.000651 mol). To this was slowly added a solution of 4-chlorobenzyl bromide (24.00 g, 0.1168 mol) in ether (100 mL). Upon addition of approximately 1 mL of solution an exotherm was noted and the mixture reached reflux. The addition of solution was slowly continued to maintain a gentle reflux (˜90 min). On completion of addition, the reaction was heated for 30 minutes at 45° C. The reaction was then cooled to 0° C. Isobutyraldehyde (12.7 mL, 0.140 mol) in ether (10 mL) was then added slowly over 2 hours. On completion of the addition the reaction was allowed to warm to 23° C. and stirred overnight. The reaction was quenched with ice (˜200 g) and acidified with 2M HCl (˜100 ml). This was extracted twice with ether and the organic phase was evaporated. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) to afford the title compound (9.89 g, 43%). the mixture reached reflux The addition of solution to maintain a gentle reflux (˜90 min) On completion of addition The reaction was then cooled to 0° C On completion of the addition the reaction to warm to 23° C. The reaction was quenched with ice (˜200 g) This was extracted twice with ether the organic phase was evaporated The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2)

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

Procedure: Concentrated sulfuric acid (45.0 mL) was added to water (5.00 mL) carefully and allowed to cool down to room temperature. 1-(4-chlorophenyl)-3-methylbutan-2-ol (17.8 g, 0.0896 mol) was added portionwise over 30 minutes. After the addition, the mixture was left to stir at room temperature for 2 hours. The mixture was then poured onto ice and the aqueous layer was extracted with ether. The organic phase was washed water and then dried over magnesium sulphate and concentrated to yield crude product. The residue was purified by filtration through a plug of silica, eluting with dichloromethane, to yield the product, 12.6 g (78%). 1H-NMR (400 MHz, CDCl3, δ): 7.10 (m, 3H), 2.85 (t, J=7.2 Hz, 1H), 1.94 (t, J=7.2 Hz, 1H), 1.25 (s, 6H). After the addition the mixture was left The mixture was then poured onto ice the aqueous layer was extracted with ether The organic phase was washed water dried over magnesium sulphate concentrated to yield crude product The residue was purified by filtration through a plug of silica eluting with dichloromethane to yield the product, 12.6 g (78%)

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (5.02 g, 0.206 mol) was covered in dry ether (50 mL, 0.5 mol) under an atmosphere of nitrogen. Iodine (0.254 g, 0.001 mol) was added to the reaction, followed by approximately 1 mL of a solution of 1-chloro-4-(chloromethyl)-benzene (32.20 g, 0.200 mol) in ether (25.0 mL, 0.238 mol). An exotherm was noted and the mixture reached reflux. The slow addition of solution was continued over 90 minutes to maintain a gentle reflux. On completion of the addition, the reaction was heated for 30 minutes at 45° C. The reaction was then cooled to 0° C. Isobutyraldehyde (25.19 mL, 0.2774 mol) in Ether (20 mL, 0.2 mol) was then added slowly over 2 hours at 0° C. On completion of the addition the reaction was allowed to warm to room temperature and stir overnight. The reaction was then quenched with ice (200 g) and acidified with 2M HCl (100 mL). The organic phase was separated and the aqueous was extracted twice with more ether. The combined organic phase was evaporated and the residue was purified by silica gel chromatography, eluting with 0 to 10% methanol in dichloromethane to yield the product, 17.8 g (45%). 1H NMR (300 MHz, CDCl3, δ): 7.22 (m, 4H), 3.56 (m, 1H), 2.81 (dd, J=3.3 Hz, 13.7 Hz, 1H), 2.58 (dd, J=9.4 Hz, 13.7 Hz, 1H), 1.74 (dt, J=6.5 Hz, 12.9 Hz, 1H), 1.45 (s, 1H), 1.00 (s, 3H), 0.98 (s, 3H). the mixture reached reflux The slow addition of solution to maintain a gentle reflux On completion of the addition The reaction was then cooled to 0° C On completion of the addition the reaction to warm to room temperature The reaction was then quenched with ice (200 g) The organic phase was separated the aqueous was extracted twice with more ether The combined organic phase was evaporated the residue was purified by silica gel chromatography eluting with 0 to 10% methanol in dichloromethane to yield the product, 17.8 g (45%)

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

Procedure: Concentrated sulfuric acid (45.0 mL) was added to water (5.00 mL) carefully and allowed to cool down to room temperature. 1-(4-chlorophenyl)-3-methylbutan-2-ol (17.8 g, 0.0896 mol) was added portionwise over 30 minutes. After the addition, the mixture was left to stir at room temperature for 2 hours. The mixture was then poured onto ice and the aqueous layer was extracted with ether. The organic phase was washed water and then dried over magnesium sulphate and concentrated to yield crude product. The residue was purified by filtration through a plug of silica, eluting with dichloromethane, to yield the product, 12.6 g (78%). 1H-NMR (400 MHz, CDCl3, δ): 7.10 (m, 3H), 2.85 (t, J=7.2 Hz, 1H), 1.94 (t, J=7.2 Hz, 1H), 1.25 (s, 6H). After the addition the mixture was left The mixture was then poured onto ice the aqueous layer was extracted with ether The organic phase was washed water dried over magnesium sulphate concentrated to yield crude product The residue was purified by filtration through a plug of silica eluting with dichloromethane to yield the product, 12.6 g (78%)

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (5.02 g, 0.206 mol) was covered in dry ether (50 mL, 0.5 mol) under an atmosphere of nitrogen. Iodine (0.254 g, 0.001 mol) was added to the reaction, followed by approximately 1 mL of a solution of 1-chloro-4-(chloromethyl)-benzene (32.20 g, 0.200 mol) in ether (25.0 mL, 0.238 mol). An exotherm was noted and the mixture reached reflux. The slow addition of solution was continued over 90 minutes to maintain a gentle reflux. On completion of the addition, the reaction was heated for 30 minutes at 45° C. The reaction was then cooled to 0° C. Isobutyraldehyde (25.19 mL, 0.2774 mol) in Ether (20 mL, 0.2 mol) was then added slowly over 2 hours at 0° C. On completion of the addition the reaction was allowed to warm to room temperature and stir overnight. The reaction was then quenched with ice (200 g) and acidified with 2M HCl (100 mL). The organic phase was separated and the aqueous was extracted twice with more ether. The combined organic phase was evaporated and the residue was purified by silica gel chromatography, eluting with 0 to 10% methanol in dichloromethane to yield the product, 17.8 g (45%). 1H NMR (300 MHz, CDCl3, δ): 7.22 (m, 4H), 3.56 (m, 1H), 2.81 (dd, J=3.3 Hz, 13.7 Hz, 1H), 2.58 (dd, J=9.4 Hz, 13.7 Hz, 1H), 1.74 (dt, J=6.5 Hz, 12.9 Hz, 1H), 1.45 (s, 1H), 1.00 (s, 3H), 0.98 (s, 3H). the mixture reached reflux The slow addition of solution to maintain a gentle reflux On completion of the addition The reaction was then cooled to 0° C On completion of the addition the reaction to warm to room temperature The reaction was then quenched with ice (200 g) The organic phase was separated the aqueous was extracted twice with more ether The combined organic phase was evaporated the residue was purified by silica gel chromatography eluting with 0 to 10% methanol in dichloromethane to yield the product, 17.8 g (45%)

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 concentrated sulfuric acid (3.00 mL, 0.056 mol) in water (0.28 mL, 0.0156 mol) was added 1-(4-chlorophenyl)-3-methylbutan-2-ol (1.00 g, 0.00503 mol) over 30 minutes. Additional sulfuric acid was added to dissolve the solid. The mixture was stirred for 2 hours. The mixture was poured onto ice then extracted with ether. The organic phase was washed (water), dried (MgSO4), filtered, and concentrated. The residue was filtered through a plug of silica with CH2Cl2 to afford the title compound (0.568 g, 63%). to dissolve the solid The mixture was poured onto ice then extracted with ether The organic phase was washed (water) dried (MgSO4) filtered concentrated The residue was filtered through a plug of silica with CH2Cl2

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of magnesium (2.98 g, 0.123 mol) in ether (30 mL) was added iodine (0.165 g, 0.000651 mol). To this was slowly added a solution of 4-chlorobenzyl bromide (24.00 g, 0.1168 mol) in ether (100 mL). Upon addition of approximately 1 mL of solution an exotherm was noted and the mixture reached reflux. The addition of solution was slowly continued to maintain a gentle reflux (˜90 min). On completion of addition, the reaction was heated for 30 minutes at 45° C. The reaction was then cooled to 0° C. Isobutyraldehyde (12.7 mL, 0.140 mol) in ether (10 mL) was then added slowly over 2 hours. On completion of the addition the reaction was allowed to warm to 23° C. and stirred overnight. The reaction was quenched with ice (˜200 g) and acidified with 2M HCl (˜100 ml). This was extracted twice with ether and the organic phase was evaporated. The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2) to afford the title compound (9.89 g, 43%). the mixture reached reflux The addition of solution to maintain a gentle reflux (˜90 min) On completion of addition The reaction was then cooled to 0° C On completion of the addition the reaction to warm to 23° C. The reaction was quenched with ice (˜200 g) This was extracted twice with ether the organic phase was evaporated The residue was purified by flash chromatography (0 to 10% MeOH/CH2Cl2)

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

Procedure: To a solution of concentrated sulfuric acid (3.00 mL, 0.056 mol) in water (0.28 mL, 0.0156 mol) was added 1-(4-chlorophenyl)-3-methylbutan-2-ol (1.00 g, 0.00503 mol) over 30 minutes. Additional sulfuric acid was added to dissolve the solid. The mixture was stirred for 2 hours. The mixture was poured onto ice then extracted with ether. The organic phase was washed (water), dried (MgSO4), filtered, and concentrated. The residue was filtered through a plug of silica with CH2Cl2 to afford the title compound (0.568 g, 63%). to dissolve the solid The mixture was poured onto ice then extracted with ether The organic phase was washed (water) dried (MgSO4) filtered concentrated The residue was filtered through a plug of silica with CH2Cl2