2-(4-chlorophenyl)-2-methylpropan-1-ol

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: A stirring mixture of 5.4 grams (0.136 mole) of lithium aluminum hydride in 300 mL of diethyl ether is cooled in an ice-water bath, and a solution of 45.0 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanoic acid in 300 mL of diethyl ether is added dropwise during a one hour period. Upon completion of addition, the reaction mixture is allowed to warm to ambient temperature where it is stirred for about 18 hours. After this time the reaction mixture is cooled in an ice-water bath, and the reaction is quenched with the careful dropwise addition of water. Upon completion of addition, the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide. The mixture is then made acidic with aqueous 2N hydrochloric acid. The organic layer is separated and dried with magnesium sulfate. The mixture is filtered and concentrated under reduced pressure, yielding 41.7 grams of 2-methyl-2-(4-chlorophenyl)propanol. The NMR spectrum is consistent with the proposed structure. is cooled in an ice-water bath Upon completion of addition After this time the reaction mixture is cooled in an ice-water bath the reaction is quenched with the careful dropwise addition of water Upon completion of addition the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide The organic layer is separated dried with magnesium sulfate The mixture is filtered concentrated under reduced pressure

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: A stirring mixture of 5.4 grams (0.136 mole) of lithium aluminum hydride in 300 mL of diethyl ether is cooled in an ice-water bath, and a solution of 45.0 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanoic acid in 300 mL of diethyl ether is added dropwise during a one hour period. Upon completion of addition, the reaction mixture is allowed to warm to ambient temperature where it is stirred for about 18 hours. After this time the reaction mixture is cooled in an ice-water bath, and the reaction is quenched with the careful dropwise addition of water. Upon completion of addition, the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide. The mixture is then made acidic with aqueous 2N hydrochloric acid. The organic layer is separated and dried with magnesium sulfate. The mixture is filtered and concentrated under reduced pressure, yielding 41.7 grams of 2-methyl-2-(4-chlorophenyl)propanol. The NMR spectrum is consistent with the proposed structure. is cooled in an ice-water bath Upon completion of addition After this time the reaction mixture is cooled in an ice-water bath the reaction is quenched with the careful dropwise addition of water Upon completion of addition the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide The organic layer is separated dried with magnesium sulfate The mixture is filtered concentrated under reduced pressure

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

Procedure: To a stirring solution of 41.7 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanol in 100 mL of dimethyl sulfoxide is added 126 mL (0.904 mole) of triethylamine. A solution of 63.0 grams (0.452 mole) of triethylamine-sulfur trioxide complex in 300 mL of dimethyl sulfoxide is then added portionwise during a 15 minute period. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about five hours. The reaction mixture is then poured into about 500 mL of ice, and made acidic with aqueous 2N hydrochloric acid. The mixture is then extracted with two 100 mL portions of diethyl ether. The combined extracts are dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 22.9 grams of 2-methyl-2-(4-chlorophenyl)propanaldehyde. The NMR spectrum is consistent with the proposed structure. Upon completion of addition The mixture is then extracted with two 100 mL portions of diethyl ether The combined extracts are dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

Procedure: A stirring mixture of 5.4 grams (0.136 mole) of lithium aluminum hydride in 300 mL of diethyl ether is cooled in an ice-water bath, and a solution of 45.0 grams (0.226 mole) of 2-methyl-2-(4-chlorophenyl)propanoic acid in 300 mL of diethyl ether is added dropwise during a one hour period. Upon completion of addition, the reaction mixture is allowed to warm to ambient temperature where it is stirred for about 18 hours. After this time the reaction mixture is cooled in an ice-water bath, and the reaction is quenched with the careful dropwise addition of water. Upon completion of addition, the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide. The mixture is then made acidic with aqueous 2N hydrochloric acid. The organic layer is separated and dried with magnesium sulfate. The mixture is filtered and concentrated under reduced pressure, yielding 41.7 grams of 2-methyl-2-(4-chlorophenyl)propanol. The NMR spectrum is consistent with the proposed structure. is cooled in an ice-water bath Upon completion of addition After this time the reaction mixture is cooled in an ice-water bath the reaction is quenched with the careful dropwise addition of water Upon completion of addition the reaction mixture is made basic with the slow addition of aqueous 10% sodium hydroxide The organic layer is separated dried with magnesium sulfate The mixture is filtered concentrated under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 15.0 g of a 50% aqueous solution of NaOH were added 6.0 g of 2-(4-chlorophenyl)-2-methylpropyl alcohol, 8.1 g of 3-(4-methylphenoxy)benzyl chloride and 1.1 g of tetrabutyl ammonium bromide, and the mixture was stirred at 80° C. for 1 hour. The mixture was cooled to room temperature and water was added, and the mixture was extracted with toluene and the toluene extract was washed with water and dried over Na2SO4, and evaporated under reduced pressure, and the obtained crude ether was purified by column chromatography on 250 g of silica gel (1:1 mixed solvent of toluene and n-hexane was used as eluent) to give 9.9 g of the desired ether (the yield was 80% of the theoretical yield). The mixture was cooled to room temperature the mixture was extracted with toluene the toluene extract was washed with water dried over Na2SO4 evaporated under reduced pressure the obtained crude ether was purified by column chromatography on 250 g of silica gel (1:1 mixed solvent of toluene and n-hexane was used as eluent) to give 9.9 g of the desired ether (the yield was 80% of the theoretical yield)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture consisting of 2.0 g of 3-(2-fluoroethoxy)benzyl chloride, 2.3 g of 2-(4-chlorophenyl)-2-methylpropyl alcohol, 0.5 g of triethylbenzylammonium bromide and 5 g of a 50% aqueous solution of sodium hydroxide was stirred at 50° C. for 2 hours. The reaction mixture was cooled to room temperature, and poured into water. Toluene was added, and the mixture was fully stirred. The toluene layer was separated, washed with water and dried over anhydrous sodium sulfate. Toluene was evaporated under reduced pressure. The resulting crude ether was purified by silica gel (100 g) column chromatography (developing solvent: toluene) to give 2.9 g of the desired 3-(2-fluoroethoxy)benzyl 2-(4-chlorophenyl)-2-methylpropyl ether. The reaction mixture was cooled to room temperature the mixture was fully stirred The toluene layer was separated washed with water dried over anhydrous sodium sulfate Toluene was evaporated under reduced pressure The resulting crude ether was purified by silica gel (100 g) column chromatography (developing solvent: toluene)

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

Procedure: To a stirring solution of oxalyl chloride (1.422 mL, 16.25 mmol) in 40 mL of dichloromethane at −5° C. was added dimethylsulfoxide (1.153 mL, 16.25 mmol) dropwise. After 15 min of stirring, a solution of 2-(4-chlorophenyl)-2-methylpropan-1-ol (1.0 g, 5.42 mmol) in 15 mL of dichloromethane was added dropwise and the resulting mixture was stirred for 30 min at the same temperature. Then triethylamine (3.02 mL, 21.66 mmol) was added and the resulting mixture was stirred for 1 hr at −20° C. with gradual warm-up to room temperature over 2 hrs. The reaction was quenched with water and extracted with ether. The organic layer was separated and washed with brine. It was then dried over anhyd. magnesium sulfate, concentrated and chromatographed using silica gel flash chromatography to yield 2-(4-chlorophenyl)-2-methylpropanal (0.82 g, 4.49 mmol, 83% yield) as a clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 9.48 (1H, s), 7.33-7.39 (2H, m), 7.21 (2H, d, J=8.79 Hz), 1.46 (6H, s). the resulting mixture was stirred for 30 min at the same temperature the resulting mixture was stirred for 1 hr at −20° C. The reaction was quenched with water extracted with ether The organic layer was separated washed with brine It was then dried over anhyd magnesium sulfate, concentrated chromatographed

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The DMSO (436 mL, 61.4 mmol) was dissolved in 100 mL of DCM and treated with oxalyl chloride (4.02 μL, 46.6 mmol) at −78° C. The solution stirred for 30 minutes at −78° C. before the 2-(4-chlorophenyl)-2-methyl-propan-1-ol (5.67 g, 30.7 mmol) was added dropwise as a solution in 10 mL of DCM. After addition was complete, the solution was stirred for two hours at −78° C., and then treated with triethyl amine (25.7 mL, 184 mmol). The solution was allowed to warm to ambient temperature and stir for three hours. The solution was quenched with the addition of water and partitioned with more DCM. The aqueous was extracted with DCM, and the combined organics were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica, hexanes/ethyl acetate gradients) to afford 2-(4-chlorophenyl)-2-methylpropionaldehyde as a yellow oil (5.60 g, 99%). 1H NMR (CDCl3, 400 MHz) δ 9.48 (s, 1H), 7.35 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.8 Hz, 1H), 1.45 (s, 6H). After addition to warm to ambient temperature stir for three hours The solution was quenched with the addition of water partitioned with more DCM The aqueous was extracted with DCM the combined organics were dried over MgSO4 filtered concentrated in vacuo The residue was purified by chromatography (silica, hexanes/ethyl acetate gradients)

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

Procedure: The 2-(4-chlorophenyl)-2-methyl-propionic acid (6.10 g, 30.7 mmol) was dissolved in 120 mL of dry THF at room temperature. A 70% w/w solution of Red-Al (28.25 mL, 0.101 mol) was added dropwise via syringe over 5 minutes (vigorous bubbling). The mixture was heated to reflux for three hours. The solution was cooled to 0 C and carefully quenched with the addition of saturated sodium tartrate solution (100 mL, violent hydrogen evolution) and 100 mL of water. The aqueous mixture was extracted with ethyl acetate, and the combined organic was washed with diluted NaHCO3 solution, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford 2-(4-chlorophenyl)-2-methyl-propan-1-ol as a colorless oil (5.70 g, 99%). The material was used without purification. 1H NMR (CDCl3, 400 MHz) δ 7.32 (s, 5H), 3.62 (d, J=4.4 Hz, 2H), 1.33 (s, 6H), 1.23 (t, J=4.4 Hz, 1H). (vigorous bubbling) The mixture was heated to reflux for three hours The solution was cooled to 0 C carefully quenched with the addition of saturated sodium tartrate solution (100 mL, violent hydrogen evolution) and 100 mL of water The aqueous mixture was extracted with ethyl acetate the combined organic was washed with diluted NaHCO3 solution brine, separated dried over MgSO4 filtered concentrated in vacuo