methyl 2-(4-fluorophenyl)-2-hydroxyacetate

Conditions: temp:3.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cool a mixture of N-methyl-O-methyl hydroxylamine hydrochloride (118 mmol) and toluene (125 mL) to −5° C. Slowly add trimethylaluminum (2 M in heptane, 59.2 mL, 118 mmol) to the mixture over 20 minutes, maintaining the reaction temperature from −1 to 8° C. After about 5 minutes slowly warm the mixture to room temperature and stir for 1.5 hours. Add a solution of methyl p-fluoromandelate (11.1 g, 60 mmol) in 75 mL of toluene over 30 min without external cooling. Cool the reaction to 0° C. and quench with 10% hydrochloric acid. Extract with ethyl acetate (4×250 mL). Wash the combined ethyl acetate layers sequentially with water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate under reduced pressure to provide 12.1 g (82%) of the desired compound. Cool After about 5 minutes slowly warm the mixture to room temperature Cool the reaction to 0° C. quench with 10% hydrochloric acid Extract with ethyl acetate (4×250 mL) Wash the combined ethyl acetate layers sequentially with water and saturated aqueous sodium chloride dry over sodium sulfate concentrate under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add potassium carbonate (12 g, 87 mmol) followed by iodomethane (7.37 mL, 118 mmol) to a 0° C. solution of p-fluoromandelic acid (79 mmol, 13.4 g) in 160 mL dry dimethylformamide under a nitrogen atmosphere. Stir the resulting mixture at 0° C. for 1 hour and at room temperature over night. Pour the reaction mixture over ice, dilute with water and ethyl acetate, and extract the aqueous layer three times with ethyl acetate. Wash the combined organic layers with cold water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate under reduced pressure to provide 12.7 g (87%) of the desired compound as a light yellow oil. at room temperature over night Pour the reaction mixture over ice extract the aqueous layer three times with ethyl acetate Wash the combined organic layers with cold water and saturated aqueous sodium chloride dry over sodium sulfate concentrate under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add potassium carbonate (12 g, 87 mmol) followed by iodomethane (7.37 mL, 118 mmol) to a 0° C. solution of p-fluoromandelic acid (79 mmol, 13.4 g) in 160 mL dry dimethylformamide under a nitrogen atmosphere. Stir the resulting mixture at 0° C. for 1 hour and at room temperature over night. Pour the reaction mixture over ice, dilute with water and ethyl acetate, and extract the aqueous layer three times with ethyl acetate. Wash the combined organic layers with cold water and saturated aqueous sodium chloride, dry over sodium sulfate and concentrate under reduced pressure to provide 12.7 g (87%) of the desired compound as a light yellow oil. at room temperature over night Pour the reaction mixture over ice extract the aqueous layer three times with ethyl acetate Wash the combined organic layers with cold water and saturated aqueous sodium chloride dry over sodium sulfate concentrate under reduced pressure