Dichloromethane → 7-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

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Reaction Steps

A solution of lithium 7-chloro-thieno[3,2-b]pyridine-2-carboxylate (15.0 g, 70.8 mmol), thionyl chloride (53.1 mL, 106.2 mmol), CH2Cl2 (600 ml), and DMF (6 ml) was heated to reflux. After 3 h the resulting yellow solution was concentrated under reduced pressure, and the residue was suspended in CH2Cl2 (500 mL). (3R)-pyrrolidin-3-ol (2.3 g, 26.2 mmol) was then added dropwise. After 12 h the reaction was quenched with 1N NaOH (500 mL), the layers were separated, and the aqueous layer was extracted with 2×500 mL CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, then concentrated under reduced pressure. The resulting solid was triturated with Et2O then collected by filtration to give a white solid (13.2 g, 70%). MS: 283.2/285.2 (MH+); HPLC Rf: 3.49 min.; HPLC purity: 99%.

Provenance & Evidence