((4-Bromobenzyl)oxy)(tert-butyl)dimethylsilane

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: A solution of 26.28 g (0.141 mol) of 4-bromobenzyl alcohol and 19.1 g (0.28 mol) of imidazole in 100 mL of methylene chloride was treated dropwise with a solution of 21.18 g (0.14 mol) of t-butyldimethylsilyl chloride in 50 mL of methylene chloride. The reaction mixture was stirred at room temperature for 30 minutes then transferred to a separatory funnel and washed with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed under vacuum giving 41 g of the product as a colorless, viscous oil. 1H NMR (200 MHz, CDCl3): 0.09 (s, 6H), 0.93 (s, 9H), 4.67 (s, 2H), 7.18 (d, 8 Hz, 2H), 7.43 (d, 8 Hz, 2H). then transferred to a separatory funnel washed with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride The organic layer was removed dried over magnesium sulfate filtered solvents removed under vacuum

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

Procedure: A solution of 26.28 g (0.141 mol) of 4-bromobenzyl alcohol and 19.1 g (0.28 mol) of imidazole in 100 mL of methylene chloride was treated dropwise with a solution of 21.18 g (0.14 mol) of t-butyldimethylsilyl chloride in 50 mL of methylene chloride. The reaction mixture was stirred at room temperature for 30 minutes then transferred to a separatory funnel and washed with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed under vacuum giving 41 g of the product as a colorless, viscous oil. 1H NMR (200 MHz, CDCl3): 0.09 (s, 6H), 0.93 (s, 9H), 4.67 (s, 2H), 7.18 (d, 8 Hz, 2H), 7.43 (d, 8 Hz, 2H). then transferred to a separatory funnel washed with water, 1N hydrochloric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride The organic layer was removed dried over magnesium sulfate filtered solvents removed under vacuum

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

Procedure: To a solution of (4-bromobenzyloxy)(tert-butyl)dimethylsilane (3.080 g) in THF (20 mL) were added Mg (0.288 g) and I2 (cat) at room temperature under an Ar atmosphere. The mixture was heated at 50° C. for 1 hour, and then cooled to room temperature. To the mixture was added 1,2-epoxypropane (0.77 mL) at room temperature under an Ar atmosphere, and the mixture was stirred at room temperature for 14.5 hours, and then heated at 50° C. for 1 hour, and then cooled to room temperature. To the mixture was added saturated aqueous NH4Cl, and the mixture was extracted with AcOEt. The organic layer was washed with saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=2/1) to afford 1-[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)phenyl]propan-2-ol (1.485 g) as a colorless oil. cooled to room temperature heated at 50° C. for 1 hour cooled to room temperature the mixture was extracted with AcOEt The organic layer was washed with saturated aqueous NaCl dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (n-hexane/AcOEt=2/1)

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

Procedure: Dissolve 4-(tert-butyldimethylsilyloxymethyl)bromobenzene (1 g, 3.319 mmol, prepared by following the procedure described in J. Am. Chem. Soc. 1995, 117, 704-714) in anhydrous THF (20 mL). Cool the solution to −78° C., add n-BuLi (4.149 mL, 6.638 mmol, 1.6M solution in hexane) and stir at this temperature for 1.5 h. Warm to −60° C., stir for an additional 30 min and add 3-pyridine carboxaldehyde. Allow the reaction mixture to warm gradually to room temperature and stir overnight. Add brine and extract with EtOAc. Dry the organic phase over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting sequentially with hexane and EtOAc to give the desired intermediate (380 mg, 35%). MS (ES+) m/z: 330 (M+H)*. prepared Warm to −60° C. stir for an additional 30 min to warm gradually to room temperature stir overnight Add brine and extract with EtOAc Dry the organic phase over Na2SO4 filter concentrate in vacuo Purify the crude mixture by chromatography on silica gel eluting sequentially with hexane and EtOAc

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

Procedure: To a dimethylformamide (30 mL) solution of (4-bromophenyl)methanol (3.00 g), imidazole (2.18 g) and tert-butyldimethylsilyl chloride (2.89 g) were added in this order. The reaction solution was stirred at room temperature for one hour. To the reaction solution, water (10 mL) was added and the aqueous layer was extracted twice with ethyl acetate (50 mL). The combined organic layer was washed in turn with 1N hydrochloric acid (10 mL) and saturated sodium chloride solution (10 mL) and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→9:1) to obtain the title compound (3.77 g) having the following physical properties. the aqueous layer was extracted twice with ethyl acetate (50 mL) The combined organic layer was washed in turn with 1N hydrochloric acid (10 mL) and saturated sodium chloride solution (10 mL) dried over anhydrous magnesium sulfate After removing the anhydrous magnesium sulfate by filtration the filtrate was concentrated The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→9:1)

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

Procedure: To a dimethylformamide (30 mL) solution of (4-bromophenyl)methanol (3.00 g), imidazole (2.18 g) and tert-butyldimethylsilyl chloride (2.89 g) were added in this order. The reaction solution was stirred at room temperature for one hour. To the reaction solution, water (10 mL) was added and the aqueous layer was extracted twice with ethyl acetate (50 mL). The combined organic layer was washed in turn with 1N hydrochloric acid (10 mL) and saturated sodium chloride solution (10 mL) and then dried over anhydrous magnesium sulfate. After removing the anhydrous magnesium sulfate by filtration, the filtrate was concentrated. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→9:1) to obtain the title compound (3.77 g) having the following physical properties. the aqueous layer was extracted twice with ethyl acetate (50 mL) The combined organic layer was washed in turn with 1N hydrochloric acid (10 mL) and saturated sodium chloride solution (10 mL) dried over anhydrous magnesium sulfate After removing the anhydrous magnesium sulfate by filtration the filtrate was concentrated The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=1:0→9:1)

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

Procedure: [(4-Bromobenzyl)oxy](tert-butyl)dimethylsilane (2.30 g, 7.64 mmol), a compound described in the literature (Eur. J. Org. Chem.; EN, 8, 2001, 1549), was dissolved in tetrahydrofuran (7.6 mL), a 1.6 M n-butyllithium-hexane solution (4.37 mL, 7.00 mmol) was added at −78° C., and the mixture was stirred at the same temperature for 30 minutes. A solution of tert-butyl {4-[methoxy(methyl)amino]-4-oxobutyl}methylcarbamate (1.65 g, 6.36 mmol), a compound described in the literature (Bio. Org. Med. Chem. 2004, 12, 5147-5160), in tetrahydrofuran (7.6 mL) was further added at −78° C., and the temperature was increased to room temperature. After the reaction was completed, a 1 N tetrabutylammonium fluoride-tetrahydrofuran solution (12.7 mL, 12.7 mmol) was added. Subsequently, 1 N hydrochloric acid was further added. A saturated aqueous sodium hydrogencarbonate solution was further added, the mixture was extracted with ethyl acetate, and the resulting organic layer was dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution solvents, n-hexane:ethyl acetate=1:1→1:2, v/v) to give the title compound (1.29 g; yield, 48%) as a yellow oily substance. a 1.6 M n-butyllithium-hexane solution (4.37 mL, 7.00 mmol) was added at −78° C. was further added at −78° C. the mixture was extracted with ethyl acetate the resulting organic layer was dried with anhydrous sodium sulfate The solvent was evaporated under reduced pressure the resulting residue was purified by silica gel column chromatography ( elution solvents, n-hexane

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

Procedure: [(4-Bromobenzyl)oxy](tert-butyl)dimethylsilane (2.30 g, 7.64 mmol), a compound described in the literature (Eur. J. Org. Chem.; EN, 8, 2001, 1549), was dissolved in tetrahydrofuran (7.6 mL), a 1.6 M n-butyllithium-hexane solution (4.37 mL, 7.00 mmol) was added at −78° C., and the mixture was stirred at the same temperature for 30 minutes. A solution of tert-butyl {4-[methoxy(methyl)amino]-4-oxobutyl}methylcarbamate (1.65 g, 6.36 mmol), a compound described in the literature (Bio. Org. Med. Chem. 2004, 12, 5147-5160), in tetrahydrofuran (7.6 mL) was further added at −78° C., and the temperature was increased to room temperature. After the reaction was completed, a 1 N tetrabutylammonium fluoride-tetrahydrofuran solution (12.7 mL, 12.7 mmol) was added. Subsequently, 1 N hydrochloric acid was further added. A saturated aqueous sodium hydrogencarbonate solution was further added, the mixture was extracted with ethyl acetate, and the resulting organic layer was dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (elution solvents, n-hexane:ethyl acetate=1:1→1:2, v/v) to give the title compound (1.29 g; yield, 48%) as a yellow oily substance. a 1.6 M n-butyllithium-hexane solution (4.37 mL, 7.00 mmol) was added at −78° C. was further added at −78° C. the mixture was extracted with ethyl acetate the resulting organic layer was dried with anhydrous sodium sulfate The solvent was evaporated under reduced pressure the resulting residue was purified by silica gel column chromatography ( elution solvents, n-hexane

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 (4-bromophenyl)methanol (3.0 g, 16.04 mmol) and imidazole (1.42 g, 20.85 mmol) in dichloromethane was added tert-butyl dimethylsilyl chloride (3.14 g, 20.85 mmol) and the mixture was stirred at room temperature overnight. The reaction was diluted with water, extracted with ethyl acetate (2×) and concentrated. The residue was absorbed onto silica and purified by flash column chromatography (silica gel, ethyl acetate/hexanes) to give the desired product. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.3 Hz, 2H), 4.68 (s, 2H), 0.94 (s, 9H), 0.09 (s, 6H). extracted with ethyl acetate (2×) concentrated The residue was absorbed onto silica purified by flash column chromatography (silica gel, ethyl acetate/hexanes)