Hydrochloric Acid → 7-fluoro-3,4-dihydro-2H-1-benzopyran-4-one

To a solution of 3-(3-fluorophenoxy)-propionic acid (4.94 g, 26.8 mmol) in dichloromethane (135 mL) is added several drops of anhydrous dimethylformamide, followed by oxalyl chloride (4.68 mL, 53.6 mmol). The reaction is stirred at room temperature until gas evolution ceases (˜30 min), then evaporated under reduced pressure and reconstituted in dichloromethane (135 mL). Following the addition of aluminum trichloride (4.28 g, 32.1 mmol), the reaction is stirred for 1 h, then 2 M aqueous hydrochloric acid (100 mL) and dichloromethane (100 mL) are added. The layers are separated, and the aqueous layer extracted with dichloromethane (2×100 mL). The combined organic-layers are washed with brine (2×100 mL), dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude residue is recrystallized twice from 2-propanol to afford slightly impure title compound (1.79 g, 40%), and the mother liquor subjected to flash chromatography (silica gel, 3:1 pentane/Et2O) to afford pure title compound (1.15 g, 26%): Rf 0.45 (1:1 ethyl acetate/hexanes); mp 53-56 ° C.; 1 H NMR (300 MHz, CDCl3), δ2.75 (t, J=6.4 Hz, 2H), 4.51 (t, J=6.4 Hz, 2H), 6.61 (dd, J=2.3, 9.9 Hz, 1H), 6.65-6.72 (m, 1H), 7.87 (dd, J=6.7, 8.8 Hz, 1H); 19F NMR (282 MHz, CDCl3), δ-101.06; APCI MS m/z 167 [C9H7FO2+H]+.

1. customevaporated under reduced pressure
2. stirringthe reaction is stirred for 1 h
3. customThe layers are separated
4. extractionthe aqueous layer extracted with dichloromethane (2×100 mL)
5. washThe combined organic-layers are washed with brine (2×100 mL)
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated under reduced pressure
9. customThe crude residue is recrystallized twice from 2-propanol

ORDレコード

ord-6293fdbd1dd74ce5b9e8214e620338e6

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07728150B2