methyl 2-(4-chlorophenyl)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:

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: Methyl 2-(4-chlorophenyl)acetate (36.7 g, 199 mmol) and paraformaldehyde (6.27 g, 209 mmol) were dissolved/suspended in DMSO (400 mL) and treated with NaOMe (537 mg, 9.94 mmol). The mixture was allowed to stir at room temperature for 2 hours to completion by thin layer chromatography (“TLC”) analysis of the crude. The reaction was poured into ice-cold water (700 mL; white emulsion) and neutralized with the addition of 1M HCl solution. The aqueous layer was extracted with ethyl acetate (3×), and the organics were combined. The organic layer was washed with water (2×), brine (1×), separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude product as an oil. The residue was loaded onto a large fritted filtered with silica gel and eluted with 9:1 hexanes:ethyl acetate until the starting material/olefin were collected. The plug was then eluted with 1:1 hexanes:ethyl acetate until the pure desired product was eluted completely. The concentrated pure fractions yielded methyl 2-(4-chlorophenyl)-3-hydroxypropanoate as an oil (39.4 g, 92%). The aqueous layer was extracted with ethyl acetate (3×) The organic layer was washed with water (2×), brine (1×) separated dried over MgSO4 filtered concentrated in vacuo to afford the crude product as an oil eluted with 9:1 hexanes ethyl acetate until the starting material/olefin were collected The plug was then eluted with 1:1 hexanes ethyl acetate until the pure desired product was eluted completely

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 solution of 102 g (0.55 mole) of methyl (4-chlorophenyl)acetate in 100 ml of carbon tetrachloride was added 97.9 g (0.55 mole) of N-bromosuccinimide. The resulting mixture was refluxed and irradiated with a 500 W bromo lamp for 5 hours. It was then cooled, filtered, and the filtrate was evaporated to dryness to give 150 g (103% yield) of methyl (4-chlorophenyl)bromoacetate. The resulting mixture was refluxed irradiated with a 500 W bromo lamp for 5 hours It was then cooled filtered the filtrate was evaporated to dryness

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

Procedure: To a solution of 100 g (0.59 mole) of 4-chlorophenylacetic acid in 165 ml of 1,2-dichloroethane and 96 ml (2.4 moles) of methanol was added 2.75 ml of concentrated sulfuric acid, and the mixture was refluxed for 6 hours. It was then cooled, poured into an aqueous sodium bicarbonate solution and stirred. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated to dryness to give 102 g (94% yield) of methyl (4-chlorophenyl)acetate. the mixture was refluxed for 6 hours It was then cooled The organic layer was separated dried over anhydrous sodium sulfate filtered the filtrate was evaporated to dryness

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

Procedure: To a solution of 4.35 g of 60% sodium hydride in 50 ml of DMF was added dropwise 20.0 g of methyl 4-chlorophenyl acetate in 25 ml of DMF. Once the evolution had ceased a mixture of 20.0 g of 2-bromoethyl benzene in 25 m of DMF was added and the reaction was stirred at room temPerature overnight. The reaction was then partitioned between 400 ml of ether and 200 ml of H2O. The ether extracts were washed with H2O, dried over magnesium sulfate, filtered and concentrated to 32.9 g of a yellow oil. Chromatography on silica gel with 5% ethyl acetate in hexane afforded 12.6 g of the title compound as a clear, colorless oil. was added The reaction was then partitioned between 400 ml of ether and 200 ml of H2O The ether extracts were washed with H2O dried over magnesium sulfate filtered concentrated to 32.9 g of a yellow oil