1-(bromomethyl)-3-ethylbenzene

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl acetoacetate (25 g) in tetrahydrofuran (800 ml) at 0° C. was added LDA (2.0M solution in heptanes/tetrahydrofuran/ethylbenzene) (194 ml). After 40 min the product from step (ii) (39 g) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was acidified with 2N HCl and the organic phase was concentrated under reduced pressure. The residue was dissolved in diethyl ether and washed with water and saturated brine. The organic phase was collected, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 5-10% ethyl acetate in isohexane. the organic phase was concentrated under reduced pressure The residue was dissolved in diethyl ether washed with water and saturated brine The organic phase was collected dried (MgSO4) evaporated under reduced pressure Purification eluting with 5-10% ethyl acetate in isohexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl acetoacetate (25 g) in tetrahydrofuran (800 ml) at 0° C. was added LDA (2.0M solution in heptanes/tetrahydrofuran/ethylbenzene) (194 ml). After 40 min the product from step (ii) (39 g) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was acidified with 2N HCl and the organic phase was concentrated under reduced pressure. The residue was dissolved in diethyl ether and washed with water and saturated brine. The organic phase was collected, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 5-10% ethyl acetate in isohexane. the organic phase was concentrated under reduced pressure The residue was dissolved in diethyl ether washed with water and saturated brine The organic phase was collected dried (MgSO4) evaporated under reduced pressure Purification eluting with 5-10% ethyl acetate in isohexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl acetoacetate (25 g) in tetrahydrofuran (800 ml) at 0° C. was added LDA (2.0M solution in heptanes/tetrahydrofuran/ethylbenzene) (194 ml). After 40 min the product from step (ii) (39 g) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was acidified with 2N HCl and the organic phase was concentrated under reduced pressure. The residue was dissolved in diethyl ether and washed with water and saturated brine. The organic phase was collected, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 5-10% ethyl acetate in isohexane. the organic phase was concentrated under reduced pressure The residue was dissolved in diethyl ether washed with water and saturated brine The organic phase was collected dried (MgSO4) evaporated under reduced pressure Purification 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: n-Butyllithium (16.8 ml of a 2.5M solution in isohexane) was added dropwise to a stirred solution of the product of step (iii) (8.13 g) in dry tetrahydrofuran (ISOml) at 0° C. under nitrogen. After 1 hour, the product of step (ii) (8.0 g) in tetrahydrofliran (60 ml) was added. After 1 hour, the reaction was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic solution was dried (MgSO4) and evaporated. Purification was by chromatography eluting with 5% ethyl acetate in isohexane. Yield 4.93 g. After 1 hour the reaction was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic solution was dried (MgSO4) evaporated Purification eluting with 5% ethyl acetate in isohexane

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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl acetoacetate (25 g) in tetrahydrofuran (800 ml) at 0° C. was added LDA (2.0M solution in heptanes/tetrahydrofuran/ethylbenzene) (194 ml). After 40 min the product from step (ii) (39 g) was added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was acidified with 2N HCl and the organic phase was concentrated under reduced pressure. The residue was dissolved in diethyl ether and washed with water and saturated brine. The organic phase was collected, dried (MgSO4) and evaporated under reduced pressure. Purification was by chromatography eluting with 5-10% ethyl acetate in isohexane. the organic phase was concentrated under reduced pressure The residue was dissolved in diethyl ether washed with water and saturated brine The organic phase was collected dried (MgSO4) evaporated under reduced pressure Purification eluting with 5-10% ethyl acetate in isohexane