methyl 2-[2-(bromomethyl)phenyl]acetate

Conditions: temp:0.00; pressure:0.00; stir:

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 mixture of 2-hydroxy6-chloropyridine (0.84 g, 6.5 mmol), sodium hydroxide (0.275 g, 6.9 mmol) and 15-crown-5 (1 drop) in dry toluene (15 ml) were stirred at reflux for 1.5 hours. The toluene was removed under reduced pressure and the white salt residue was dissolved in dry DMF (10 ml). Methyl 2-bromomethylphenylacetate (1.5 g, 6.2 mmol) in dry DMF (10 ml) was added dropwise along with sodium iodide (10 mg). The mixture was stirred at room temperature for 2 hours, poured into water and extracted with diethyl ether. The ether extracts were washed with water, dried and the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane) to give methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate (1.11 g, 61%) (Compound No. 1 in Table 1) as a pale yellow oil; 1H NMR(270 MHz)δ:3.67(3H,s), 3.82(2H,s), 5.39(2H,s) 6.65(1H,d), 6.90(1H,d), 7.25-7.55(5H,m) ppm. at reflux for 1.5 hours The toluene was removed under reduced pressure the white salt residue was dissolved in dry DMF (10 ml) The mixture was stirred at room temperature for 2 hours extracted with diethyl ether The ether extracts were washed with water dried the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane)

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

Procedure: A mixture of 2-hydroxy6-chloropyridine (0.84 g, 6.5 mmol), sodium hydroxide (0.275 g, 6.9 mmol) and 15-crown-5 (1 drop) in dry toluene (15 ml) were stirred at reflux for 1.5 hours. The toluene was removed under reduced pressure and the white salt residue was dissolved in dry DMF (10 ml). Methyl 2-bromomethylphenylacetate (1.5 g, 6.2 mmol) in dry DMF (10 ml) was added dropwise along with sodium iodide (10 mg). The mixture was stirred at room temperature for 2 hours, poured into water and extracted with diethyl ether. The ether extracts were washed with water, dried and the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane) to give methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate (1.11 g, 61%) (Compound No. 1 in Table 1) as a pale yellow oil; 1H NMR(270 MHz)δ:3.67(3H,s), 3.82(2H,s), 5.39(2H,s) 6.65(1H,d), 6.90(1H,d), 7.25-7.55(5H,m) ppm. at reflux for 1.5 hours The toluene was removed under reduced pressure the white salt residue was dissolved in dry DMF (10 ml) The mixture was stirred at room temperature for 2 hours extracted with diethyl ether The ether extracts were washed with water dried the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane)

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

Procedure: 5.12 g of o-cresol and 7.2. g of pulverized potash in 30 ml of acetonitrile are preheated to 60° C. and a solution of 11.06 g of 2-(bromomethyl)-phenylacetic acid methyl ester in 35 ml of acetonitrile is added dropwise over a period of 8 minutes. The reaction mixture is then stirred for 4 minutes and immediately poured onto ice-water and weakly acidified with 2N hydrochloric acid. The aqueous solution is extracted exhaustively with ethyl acetate and the combined organic phases are washed with water, dried over sodium sulfate, filtered and concentrated by evaporation. Chromatography on silica gel with hexane/ethyl acetate (9:1) yields pure 2-(2-methylphenoxymethyl)-phenylacetic acid methyl ester in the form of a pale yellow oil. are preheated to 60° C. immediately poured onto ice-water The aqueous solution is extracted exhaustively with ethyl acetate the combined organic phases are washed with water dried over sodium sulfate filtered concentrated by evaporation

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: To an ice-cold solution of (2-bromomethylphenyl)acetic acid (1 g, 4.4 mmol) in THF (2.4 mL) was added trimethylsilyldiazomethane (3 mL of a 2 M solution in hexanes, 6 mmol), and the reaction mixture was stirred for 14 h. The reaction was quenched with AcOH, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 98:2 to 94:6 methylene chloride/hexanes) afforded methyl (2-bromomethylphenyl)acetate as a light yellow solid (0.34 g, 32%): 1H NMR (300 MHz, CDCl3) δ 7.40-7.20 (m, 4H), 4.59 (s, 2H), 3.81 (s 2H), 3.71 (s, 3H). The reaction was quenched with AcOH the solvent was removed under reduced pressure Purification by flash column chromatography (silica, eluent 98:2 to 94:6 methylene chloride/hexanes)

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

Procedure: To an ice-cold solution of (2-bromomethylphenyl)acetic acid (1 g, 4.4 mmol) in THF (2.4 mL) was added trimethylsilyldiazomethane (3 mL of a 2 M solution in hexanes, 6 mmol), and the reaction mixture was stirred for 14 h. The reaction was quenched with AcOH, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, eluent 98:2 to 94:6 methylene chloride/hexanes) afforded methyl(2-bromomethylphenyl)acetate as a light yellow solid (0.34 g, 32%): 1H NMR (300 MHz, CDCl3) δ 7.40-7.20 (m, 4H), 4.59 (s, 2H), 3.81 (s 2H), 3.71 (s, 3H). The reaction was quenched with AcOH the solvent was removed under reduced pressure Purification by flash column chromatography (silica, eluent 98:2 to 94:6 methylene chloride/hexanes)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 102 g (0.74 mol) of benzohydroxamic acid 2, 111 g (0.80 mol) of pulverised potassium carbonate and 1400 ml of acetonitrile is heated to 60° C. After 0.5 h, 162 g of methyl o-bromomethylphenylacetate 1, which is obtained as 68% crude product from the bromination of methyl o-tolylacetate with N-bromosuccinimide, dissolved in 100 ml of acetonitrile, is added dropwise over 0.5 h at 60° C.-65° C. and the reaction mixture is stirred for 5.5 h at this temperature.

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

Procedure: A mixture of 2-hydroxy6-chloropyridine (0.84 g, 6.5 mmol), sodium hydroxide (0.275 g, 6.9 mmol) and 15-crown-5 (1 drop) in dry toluene (15 ml) were stirred at reflux for 1.5 hours. The toluene was removed under reduced pressure and the white salt residue was dissolved in dry DMF (10 ml). Methyl 2-bromomethylphenylacetate (1.5 g, 6.2 mmol) in dry DMF (10 ml) was added dropwise along with sodium iodide (10 mg). The mixture was stirred at room temperature for 2 hours, poured into water and extracted with diethyl ether. The ether extracts were washed with water, dried and the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane) to give methyl 2-(6-chloropyrid-2-yloxymethyl)phenylacetate (1.11 g, 61%) (Compound No. 1 in Table 1) as a pale yellow oil; 1H NMR(270 MHz)δ:3.67(3H,s), 3.82(2H,s), 5.39(2H,s) 6.65(1H,d), 6.90(1H,d), 7.25-7.55(5H,m) ppm. at reflux for 1.5 hours The toluene was removed under reduced pressure the white salt residue was dissolved in dry DMF (10 ml) The mixture was stirred at room temperature for 2 hours extracted with diethyl ether The ether extracts were washed with water dried the ether removed in vacuo leaving a yellow oil which was purified by column chromatography (silica eluted with 10 % ethyl acetate in hexane)