Phosphorus oxychloride → 7-Chlorothieno[3,2-b]pyridine

Participants

Reaction Steps

To a stirred solution of POCl3 (28.6 mL, 313 mmol) in 1,2-dichloroethane (200 mL) was added commercially available thieno[3,2-b]pyridin-7-ol (94.7 g, 626 mmol) as a powder in one portion. The reaction was stirred for 2 hours at reflux under N2. The mixture was concentrated, using toluene (3×100 mL) to azeotrope. The dark residue was resuspended in CH2Cl2 (1 L), and a saturated aqueous solution of NaHCO3 (500 mL) was carefully added. The mixture was stirred for 30 minutes until bubbling had ceased. The biphase was separated, and the aqueous was re-extracted with CH2Cl2 (500 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated, to obtain a brown oil, which crystallized upon standing (38.4 g, 71%). 7-Chlorothieno[3,2-b]pyridine has also been prepared using oxalyl chloride (WO 99/24440). 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J=5 Hz, 1H), 7.80 (d, J=6 Hz, 1H), 7.60 (d, J=6 Hz, 1H), 7.29 (d, J=5 Hz, 1H).

Provenance & Evidence