Triethylamine → HCID 68997336, compound

Participants

Reaction Steps

To an ice-cold suspension of tetrahydro-2H-pyran-4-carboxylic acid (0.65 g, 5.0 mmol) in dichloromethane (20 mL) was added oxalyl chloride (0.47 mL, 5.0 mmol) dropwise followed by a few drops of anhydrous DMF. After the ice-water bath was removed, the mixture was stirred for 1 h. To the above solution was added 2-amino-3-hydroxybenzoic acid hydrobromide (1.17 g, 5.0 mmol) followed by triethylamine (2.09 mL, 15.0 mmol). The resulting reaction mixture was stirred at room temperature for 17 h. The reaction was quenched with 1 N HCl (20 mL) and extracted with dichloromethane. The aqueous phase was further extracted with dichloromethane (2×200 mL). The combined organic phase was washed with water (2×100 mL), dried (Na2SO4), filtered and concentrated to afford a light yellow solid. The crude solid was dissolved in toluene (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (1.42 g, 7.46 mmol). The reaction mixture was then heated to reflux under nitrogen for 10 h. The reaction was cooled to room temperature, poured into water and extracted with ethyl acetate (2×250 mL). The organic phase was separated, washed with water, brine, dried (Na2SO4), filtered and concentrated to afford the 2-(tetrahydro-2H-pyran-4-yl)benzoxazole-4-carboxylic acid (590 mg, 49%) as a light brown solid: 1H NMR (500 MHz, DMSO-d6) δ 12.90 (br s, 1H), 7.93 (dd, J=7.9, 1.0 Hz, 1H), 7.86 (dd, J=7.9, 1.0 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 3.97-3.92 (m, 2H), 3.55-3.48 (m, 2H), 3.38-3.30 (m, 1H), 2.07-2.02 (m, 2H), 1.92-1.82 (m, 2H); MS (ESI+) m/z 248 (M+H).

Provenance & Evidence