Dichloromethane → 7-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O-:13])=O)[S:10][C:3]=12.[Li+].S(Cl)(Cl)=O.C(Cl)Cl.[NH:22]1[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]1>CN(C=O)C>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:11]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:8]=2)=[O:13])[CH2:23]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
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%.
Workup
- concentrationAfter 3 h the resulting yellow solution was concentrated under reduced pressure
- customAfter 12 h the reaction was quenched with 1N NaOH (500 mL)
- customthe layers were separated
- extractionthe aqueous layer was extracted with 2×500 mL CH2Cl2
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe resulting solid was triturated with Et2O
- filtrationthen collected by filtration
Sources & evidence
- ORD record
- ord-68cbf7c86b8241b29b25fa99417a8395
- Source dataset
- uspto-grants-2006_02
- Patent number
- US06995171B2
Reaction notes
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