Overview[1]
4-Benzopyranone-2-carboxylic acid is a carboxylic acid organic compound and can be used as a pharmaceutical synthesis intermediate.
Preparation[1]
4-Benzopyranone-2-carboxylic acid is prepared as follows:
1) 4-oxo-4H-benzopyran-2-carboxylic acid: within 20 minutes, mix diethyl oxalate (110mL, 810mmol) and 2′-hydroxyacetophenone (44mL, 365mmol) The mixture was added to a solution of sodium ethoxide (76 g, 1.11 mol) in ethanol (600 mL). The mixture was heated to 80°C for 1 hour and then cooled to room temperature. Water (500 mL) and diethyl ether (600 mL) were added and the mixture was acidified to pH=2 with concentrated HCl. The organic phase was separated and the aqueous phase was further extracted with diethyl ether (2X). The combined organic phases were washed with saturated aqueous sodium chloride solution (2X), dried (MgSO4) and concentrated to give an oily brown solid. The solid was mixed with glacial acetic acid (440 mL) and concentrated HCl (110 mL) and heated to 85°C overnight. The mixture was cooled to room temperature, diluted with water (550 mL) and filtered. The solid was washed with water (2 x 125 mL) and dried in a vacuum kettle to give a purple solid (58 g, 83%). Mp260-261℃; 1HNMR (300HMz, DMSO-d6) δ8.03 (m, 1H), 7.85 (m, 1H), 7.71 (m, 1H), 7.51 (m, 1H), 6.89 (s, 1H).
2) In a Parr hydrogenation apparatus, place the compound from step 1) (20.0g, 105mmol) in acetic acid (200mL) and palladium on 10% activated carbon (2g) under hydrogen pressure (60psig) . After 22.5 hours, the mixture was removed from the hydrogen atmosphere and filtered through a pad of celite. The celite pad was washed with ethyl acetate (800 mL) and the combined filtrate was concentrated to give a brown oil. The oil was dissolved in ethyl acetate (500 mL) and extracted with saturated NaHCO3 (4×125 mL). The aqueous phase was acidified with concentrated HCl to pH=2 and extracted with ethyl acetate (4×100 mL). The combined organic phases were washed with saturated aqueous sodium chloride solution (100 mL), dried (MgSO4) and concentrated to give 4-benzopyrone-2-carboxylic acid as a colorless solid (18.0 g, 96%). Mp97.5-99℃; 1HNMR (300HMz, DMSO-d6) δ12.96 (brs, 1H), 7.03 (m, 2H), 6.78 (m, 2H), 4.74 (dd, J=6.4Hz, J=3.9 Hz, 1H), 2.73 (m, 1H), 2.63 (m, 1H), 2.03 (m, 2H).
Main reference materials
[1] CN98813619.8 Carboxy-substituted chroman derivatives used as β3 adrenergic receptor agonists
