1-(4-chlorophenyl)-2-methoxyethanone

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

Procedure: To 25 g (281 mmole) of methoxyacetonitrile in 100 ml of diethyl ether at reflux was added 250 ml (250 mmole) of 1.0M 4-chlorophenyl magnesium bromide in diethyl ether. After refluxing for 30 minutes the reaction mixture was hydrolyzed with a solution of 30 ml of concentrated sulfuric acid in 100 ml of water. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and dissolved in hexanes. The insolubles were filtered away and the resultant solution was concentrated and distilled yielding a clear liquid. bp 105°-115° C. at 1 torr. The oil solidified on standing. After refluxing for 30 minutes the reaction mixture The organic layer was washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo dissolved in hexanes The insolubles were filtered away the resultant solution was concentrated distilled yielding a clear liquid

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

Procedure: Sodium borohydride (111 mg, 2.9 mmol) was added in portions to a solution of 1-(4-chlorophenyl)-2-methoxy-ethanone (1 g, 6.4 mmol) in methanol at room temperature. After 1 hour, reaction was quenched with 3 mls (aq) sat. NH4Cl. Water was added to dissolve the inorganic and mixture was extracted with ethyl acetate 3×5 ml. Combined organics were washed with brine (2×3 ml) and dried over MgSO4. Crude material was obtained upon filtration and concentration to an amber oil which was purified by flash silica gel and eluted with 10-17% EA/Hex gradient. 1-(4-chlorophenyl)-2-methoxy-ethan-1-ol was obtained as an amber oil (370 mg, 68% yield). reaction was quenched with 3 mls (aq) sat. NH4Cl Water was added to dissolve the inorganic and mixture was extracted with ethyl acetate 3×5 ml Combined organics were washed with brine (2×3 ml) dried over MgSO4 Crude material was obtained upon filtration and concentration to an amber oil which was purified by flash silica gel eluted with 10-17% EA/Hex gradient

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

Procedure: Equipped with magnetic stirring, (methoxymethyl)-triphenylphosphonium chloride (5.2 g, 15.2 mmol) was suspended in anhydrous tetrahydrofuran at 0° C. under N2 flow. Phenyl lithium, in 1.8 M in di-n-butyl ether (8.4 mL, 15.2 mmol), was added such that the temperature did not exceed 4° C. Mixture remained at 0° C. for 15 minutes, and a solution of 4-chlorobenzonitrile (0.56 g, 4.07 mmol) dissolved in 10 mls of anhydrous tetrahydrofuran was added over 15 minutes. Reaction was warmed to room temperature and continued for another 2 hours. Reaction was quenched with 50 ml of water and mixture was extracted (3×100 mls) with ether. Combined ethers were washed (2×20 mls) brine, and dried over MgSO4. Organics were filtered and concentrated to an amber oil. Oil was loaded on a flash silica gel column and eluted with 10-40% EA/Hex gradient to afford 382 mg of 1-(4-chlorophenyl)-2-methoxy-ethanone. (51% yield). did not exceed 4° C was added over 15 minutes Reaction continued for another 2 hours Reaction was quenched with 50 ml of water and mixture was extracted (3×100 mls) with ether Combined ethers were washed (2×20 mls) brine dried over MgSO4 Organics were filtered concentrated to an amber oil eluted with 10-40% EA/Hex gradient

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

Procedure: Sodium borohydride (111 mg, 2.9 mmol) was added in portions to a solution of 1-(4-chlorophenyl)-2-methoxy-ethanone (1 g, 6.4 mmol) in methanol at room temperature. After 1 hour, reaction was quenched with 3 mls (aq) sat. NH4Cl. Water was added to dissolve the inorganic and mixture was extracted with ethyl acetate 3×5 ml. Combined organics were washed with brine (2×3 ml) and dried over MgSO4. Crude material was obtained upon filtration and concentration to an amber oil which was purified by flash silica gel and eluted with 10-17% EA/Hex gradient. 1-(4-chlorophenyl)-2-methoxy-ethan-1-ol was obtained as an amber oil (370 mg, 68% yield). reaction was quenched with 3 mls (aq) sat. NH4Cl Water was added to dissolve the inorganic and mixture was extracted with ethyl acetate 3×5 ml Combined organics were washed with brine (2×3 ml) dried over MgSO4 Crude material was obtained upon filtration and concentration to an amber oil which was purified by flash silica gel eluted with 10-17% EA/Hex gradient

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

Procedure: Equipped with magnetic stirring, (methoxymethyl)-triphenylphosphonium chloride (5.2 g, 15.2 mmol) was suspended in anhydrous tetrahydrofuran at 0° C. under N2 flow. Phenyl lithium, in 1.8 M in di-n-butyl ether (8.4 mL, 15.2 mmol), was added such that the temperature did not exceed 4° C. Mixture remained at 0° C. for 15 minutes, and a solution of 4-chlorobenzonitrile (0.56 g, 4.07 mmol) dissolved in 10 mls of anhydrous tetrahydrofuran was added over 15 minutes. Reaction was warmed to room temperature and continued for another 2 hours. Reaction was quenched with 50 ml of water and mixture was extracted (3×100 mls) with ether. Combined ethers were washed (2×20 mls) brine, and dried over MgSO4. Organics were filtered and concentrated to an amber oil. Oil was loaded on a flash silica gel column and eluted with 10-40% EA/Hex gradient to afford 382 mg of 1-(4-chlorophenyl)-2-methoxy-ethanone. (51% yield). did not exceed 4° C was added over 15 minutes Reaction continued for another 2 hours Reaction was quenched with 50 ml of water and mixture was extracted (3×100 mls) with ether Combined ethers were washed (2×20 mls) brine dried over MgSO4 Organics were filtered concentrated to an amber oil eluted with 10-40% EA/Hex gradient

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

Procedure: To 25 g (281 mmole) of methoxyacetonitrile in 100 ml of diethyl ether at reflux was added 250 ml (250 mmole) of 1.0M 4-chlorophenyl magnesium bromide in diethyl ether. After refluxing for 30 minutes the reaction mixture was hydrolyzed with a solution of 30 ml of concentrated sulfuric acid in 100 ml of water. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, concentrated in vacuo, and dissolved in hexanes. The insolubles were filtered away and the resultant solution was concentrated and distilled yielding a clear liquid. bp 105°-115° C. at 1 torr. The oil solidified on standing. After refluxing for 30 minutes the reaction mixture The organic layer was washed with water and brine dried over anhydrous magnesium sulfate concentrated in vacuo dissolved in hexanes The insolubles were filtered away the resultant solution was concentrated distilled yielding a clear liquid