(3-ethylphenyl)methanol

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran (320 ml) at −78° C. After 1 hour N,N-dimethylformamide (15 ml) was added. The mixture was stirred at −78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran (320 ml) at −78° C. After 1 hour N,N-dimethylformamide (15 ml) was added. The mixture was stirred at −78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran (320 ml) at −78° C. After 1 hour N,N-dimethylformamide (15 ml) was added. The mixture was stirred at −78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: Bromine (0.21 mL, 4.08 mmol) was added dropwise to a solution of triphenylphosphine (1.08 g, 4.12 mmol) and imidazole (280 mg, 4.11 mmol) in CH2Cl2 (13.5 mL) at 0° C. The mixture was allowed to warm to room temperature and then a solution of (3-ethylphenyl)methanol (˜3.05 mmol) in CH2Cl2 (3.5 mL) was added. After 1 h, the mixture was diluted with hexanes and filtered through celite, washing with excess hexanes. The filtrate was concentrated in vacuo. Purification of the crude residue by chromatography on silica gel (hexanes→10% EtOAc/hexanes, gradient) afforded 530 mg (87% over two steps) of 1-(bromomethyl)-3-ethylbenzene. filtered through celite washing with excess hexanes The filtrate was concentrated in vacuo Purification of the crude residue by chromatography on silica gel (hexanes→10% EtOAc/hexanes, gradient)

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

Procedure: Lithium aluminum hydride (3.1 mL of 1.0 M solution in THF, 3.1 mmol) was added to a solution of methyl 3-ethylbenzoate (500 mg, 3.05 mmol) in THF (12 mL) at 0° C. After 2 h at 0° C., the reaction was quenched by the addition of saturated aqueous Rochelle's salt (50 mL) and stirred vigorously overnight at room temperature. The reaction mixture was extracted with Et2O (3×100 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo to afford (3-ethylphenyl)methanol which was shown to be ˜90% pure by 1H NMR analysis and was taken on without further purification. the reaction was quenched by the addition of saturated aqueous Rochelle's salt (50 mL) The reaction mixture was extracted with Et2O (3×100 mL) The combined organic phase was dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: Phosphorous tribromide (5.3 ml) was added to a solution of the product from step (i) (7.6 g) in benzene (150 ml) at 0° C. After 3 hours, water (40 ml) was added and the mixture warmed to room temperature and extracted with ethyl acetate. The organic phase was dried (MgSO4) and evaporated. Purified by chromatography eluting with 2% ethyl acetate in isohexane. Yield 8.0 g. extracted with ethyl acetate The organic phase was dried (MgSO4) evaporated Purified by chromatography eluting with 2% ethyl acetate in isohexane

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuiran (320 ml) at -78° C. After 1 hour dimethylformamide (15 ml) was added. The mixture was stirred at -78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. Yield 7.6 g. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran at -78° C. After 1 hour dimethylformamide (15 ml) was added. The mixture was stirred at -78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. Yield 7.6 g. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran (320 ml) at −78° C. After 1 hour N,N-dimethylformamide (15 ml) was added. The mixture was stirred at −78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane