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

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%.

1. concentrationAfter 3 h the resulting yellow solution was concentrated under reduced pressure
2. customAfter 12 h the reaction was quenched with 1N NaOH (500 mL)
3. customthe layers were separated
4. extractionthe aqueous layer was extracted with 2×500 mL CH2Cl2
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe resulting solid was triturated with Et2O
9. filtrationthen collected by filtration

ORD record

ord-68cbf7c86b8241b29b25fa99417a8395

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06995171B2