methyl 2-(4-chlorophenyl)-2-hydroxyacetate

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 a stirred solution of 4-chloromandelic acid (10.7 g, 57.3 mmol) in methanol was added sulfuric acid (3.3 mL, 63.1 mmol). The reaction mixture was refluxed for 6 hours. The reaction mixture was concentrated, neutralized with sat. sodium carbonate solution, extracted with ether, washed with brine, dried, and concentrated. Purification by silica gel chromatography (40% ethyl acetate in hexanes) yielded 10.3 g of (4-chlorophenyl)hydroxyacetic acid methyl ester. The reaction mixture was refluxed for 6 hours The reaction mixture was concentrated extracted with ether washed with brine dried concentrated Purification by silica gel chromatography (40% ethyl acetate in hexanes)

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

Procedure: To a stirred solution of 4-chloromandelic acid (10.0 g, 53.6 mmol) in methanol was added sulfuric acid (3.1 mL, 58.9 mmol). The reaction mixture was refluxed for 6 hours. The reaction mixture was concentrated, neutralized with sat. sodium carbonate solution, extracted with ether, washed with brine, dried, and concentrated. Purification by silica gel chromatography (40% ethyl acetate in hexanes) yielded 10.0 g of (4-chlorophenyl)hydroxyacetic acid methyl ester. The reaction mixture was refluxed for 6 hours The reaction mixture was concentrated extracted with ether washed with brine dried concentrated Purification by silica gel chromatography (40% ethyl acetate in hexanes)

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

Procedure: 2-(4-Chlorophenyl)-2-hydroxyacetic acid (40 g; 0.2 mol) is dissolved in 100 ml of methanol and stirred at +20° C. At this temperature 5 ml of concentrated sulfuric acid are added dropwise. After the addition is complete the reaction mixture is heated up to +45° C. and stirred for further 30 minutes. Then the reaction mixture is poured into a cooled (0° C.) solution of sodium carbonate (42 g; 0.4 mol) in 300 ml of water. The product is extracted with toluene (3×50 ml) washed with brine (3×50 ml) dried (Na2SO4) and evaporated. After crystallization from diethylether/hexane (10 g/80 g) 2-(4-chlorophenyl)-2-hydroxyacetic acid methylester (34 g; 84% yield) is obtained as a colorless solid. M.p. 54-55° C. After the addition is heated up to +45° C. stirred for further 30 minutes Then the reaction mixture is poured into The product is extracted with toluene (3×50 ml) washed with brine (3×50 ml) dried (Na2SO4) evaporated

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

Procedure: A 250 mL round bottom flask containing 5.6 g (30 mmol) of p-chlorophenyl-α-hydroxyacetic acid and 100 mL of concentrated HCl:MeOH (1:9) was warmed to reflux for 12 hours. The solution was concentrated under reduced pressure, diluted with 250 mL of Et2O and washed once with 30 mL of H2O, twice with 30 mL of NaHCO3 solution, once with 30 mL of H2O and once with 30 mL of brine. The organic layer was dried (Na2SO4) and concentrated leaving 5.0 g (83%) of methyl p-chlorophenyl-α-hydroxyacetate lit m.p. 55° C.) was warmed to reflux for 12 hours The solution was concentrated under reduced pressure diluted with 250 mL of Et2O washed once with 30 mL of H2O, twice with 30 mL of NaHCO3 solution, once with 30 mL of H2O and once with 30 mL of brine The organic layer was dried (Na2SO4) concentrated

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

Procedure: A 250 mL round bottom flask containing 5.6 g (30 mmol) of p-chlorophenyl-α-hydroxyacetic acid and 100 mL of concentrated HCl:MeOH (1:9) was warmed to reflux for 12 hours. The solution was concentrated under reduced pressure, diluted with 250 mL of Et2O and washed once with 30 mL of H2O, twice with 30 mL of NaHCO3 solution, once with 30 mL of H2O and once with 30 mL of brine. The organic layer was dried (Na2SO4) and concentrated leaving 5.0 g (83%) of methyl p-chlorophenyl-α-hydroxyacetate lit m.p. 55° C.) 1H-NMR (CDCl3) δ7.36-7.28 (m, 4H), 5.13 (s, 1 H), 3.72 (s, 3H), 3.67 (br s, 1 H (exchanges with D2O)). was warmed to reflux for 12 hours The solution was concentrated under reduced pressure diluted with 250 mL of Et2O washed once with 30 mL of H2O, twice with 30 mL of NaHCO3 solution, once with 30 mL of H2O and once with 30 mL of brine The organic layer was dried (Na2SO4) concentrated

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

Procedure: To a stirred solution of 4-chloromandelic acid (10.7 g, 57.3 mmol) in methanol was added sulfuric acid (3.3 mL, 63.1 mmol). The reaction mixture was refluxed for 6 hours. The reaction mixture was concentrated, neutralized with sat. sodium carbonate solution, extracted with ether, washed with brine, dried, and concentrated. Purification by silica gel chromatography (40% ethyl acetate in hexanes) yielded 10.3 g of (4-chlorophenyl)hydroxyacetic acid methyl ester. The reaction mixture was refluxed for 6 hours The reaction mixture was concentrated extracted with ether washed with brine dried concentrated Purification by silica gel chromatography (40% ethyl acetate in hexanes)

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

Procedure: To a stirred solution of 4-chloromandelic acid (10.0 g, 53.6 mmol) in methanol was added sulfuric acid (3.1 mL, 58.9 mmol). The reaction mixture was refluxed for 6 hours. The reaction mixture was concentrated, neutralized with sat. sodium carbonate solution, extracted with ether, washed with brine, dried, and concentrated. Purification by silica gel chromatography (40% ethyl acetate in hexanes) yielded 10.0 g of (4-chlorophenyl)hydroxyacetic acid methyl ester. The reaction mixture was refluxed for 6 hours The reaction mixture was concentrated extracted with ether washed with brine dried concentrated Purification by silica gel chromatography (40% ethyl acetate in hexanes)