Hydrochloric Acid → 1-(4-hydroxy-3-iodophenyl)ethanone

To a solution of 4-hydroxyacetophenone (4.0 g, 30 mmol) in 50% (v/v) of ammonium hydroxide (250 mL) at room temperature was quickly added a solution of potassium iodide (24.2 g, 146 mmol) and iodine (7.66 g, 30 mmol) in water (300 mL). The resulting mixture was stirred at room temperature for 14 hours and then passed through a celite pad. The filtrate was cooled to 10° C. and acidified slowly with HCl (12 N) to pH=1. The yellow precipitate was collected by filtration, washed with water to get 4-hydroxy-3-iodoacetophenone (6.3 g, 80%). A solution of 4-hydroxy-3-iodoacetophenone (3 g, 11.5 mmol) and 2-thiophenylboronic acid (1.46 g, 11.5 mmol) in DMF (50 mL) was mixed with potassium carbonate (3.16 g, 22.9 mmol) and Pd(dppf)2 (0.25 g, 0.344 mmol). The mixture was stirred at 90° C. for 14 hours, cooled to room temperature and passed through a celite pad. The filtrate was diluted with water and extracted with EtOAc (3×100 mL). The residue after concentration was purified by column (SiO2, Hexanes/EtOAc=4:1) to provide 4-hydroxy-3-(2-thiophenyl)acetophenone (1.1 g, 44%) as a light yellow solid. To a solution of 4-hydroxy-3-(2-thiophenyl)acetophenone (0.5 g, 2.29 mmol) in THF (50 mL) at −78° C. was added LDA in heptane-THF (2.6 mL, 4.7 mmol) and the solution was stirred for 1 hours. 2-Chloronicotinyl chloride (0.202 g, 1.15 mmol) was added and the resulting mixture was stirred at −78° C. for 1 h and 1 h at room temperature. The reaction was quenched with aqueous HCl (0.5 N) and extracted with CH2Cl2 (×3×100 mL). The residue after concentration was purified by column (SiO2, Hexanes/EtOAc=2:1) to provide the corresponding diketone (0.31 g, 76%). The above diketone (0.28 g, 0.78 mmol) was dissolved in HOAc (50 mL) and stirred at, 10° C. for 2 hours. It was poured into icy water. The solid was collected by filtration, washed with CH2Cl2 to afford 2-(4-hydroxy-3-(thiophen-2-yl)phenyl)-4H-pyrano[2,3-b]pyridin-4-one (0.146 g, 58%) as a grey solid; MS (ES) m/z: 322.93 (M+1), 321.93 (M); MP 273.5-275° C.

1. temperatureThe filtrate was cooled to 10° C.
2. filtrationThe yellow precipitate was collected by filtration
3. washwashed with water

ORD record

ord-7552f6a92c46490da76a8e5d503897e1

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410109B2