Sodium Chloride → (R)-1-(pyrrolidin-3-yl)piperidine

A solution of (R)-1-(pyrrolidin-3-yl)piperidine dihydrochloride (Reference Example 5c) in a minimum of water was treated with excess solid sodium hydroxide and sodium chloride. This mixture was extracted with dichloromethane. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give (R)-1-(pyrrolidin-3-yl)piperidine as the free base (308 mg, 2.0 mmol). This free base diamine was added to a stirred solution of 4-bromo-2-fluorophenylisothiocyanate (0.464 g, 2.0 mmol) in acetonitrile (20 mL). Cesium carbonate (2.6 g, 8.0 mmol) was added to the reaction mixture. The reaction mixture was then heated to 150° C. under microwave irradiation for 30 minutes. The reaction mixture was cooled to room temperature then diluted with water and extracted with chloroform. The organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give a residue that was purified by silica gel chromatography (100% dichloromethane to 50:50 dichloromethane/90% dichloromethane and 10% methanol). Fractions containing product were combined and concentrated under reduced pressure to give (R)-6-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole.

1. extractionThis mixture was extracted with dichloromethane
2. dry with materialThe organic layer was dried (MgSO4)
3. filtrationfiltered
4. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-c2417373d8e14535918ea9bcfdc561b8

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580968B2