反应详情

Under nitrogen atmosphere, 1300 mL (2.60 mol, 1.00 eq) of 2.0M methylmagnesium chloride-tetrahydrofuran solution was cooled, and 322.7 g (2.60 mol, 1.00 eq) of 2-fluorobenzaldehyde was added while adjusting the inside temperature to −20 to +2° C., followed by stirring for 30 minutes under a cooled condition in iced water. Conversion of methylation was 99.9% by determination by gas chromatography. Subsequently, while adjusting the inside temperature to −22 to 0° C., 385.1 g (2.60 mol, 1.00 eq) of phthalic anhydride was added, followed by stirring at room temperature through the night. Conversion of acylation was 99% or greater by determination by 1H-NMR. 1300 mL (2.60 mol, 1.00 eq) of 2.0N hydrochloric acid was added to the reaction-terminated liquid, followed by extraction with 650 mL of toluene. The recovered organic layer was washed with 650 mL of brine, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and vacuum dried, thereby obtaining 706.1 g of racemic 1-(2-fluorophenyl)ethyl alcohol phthalate half ester represented by the following formula,

1. customto −20 to +2° C.
2. customto −22 to 0° C.
3. additionwas added to the reaction-terminated liquid
4. extractionfollowed by extraction with 650 mL of toluene
5. washThe recovered organic layer was washed with 650 mL of brine
6. dry with materialdried with anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure, and vacuum
8. customdried