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 is treated with excess solid sodium hydroxide and sodium chloride. This mixture is extracted with dichloromethane. The organic layer is dried (MgSO4) and filtered. The filtrate is concentrated under reduced pressure to give (R)-1-(pyrrolidin-3-yl)piperidine as the free base oil (308 mg, 2.0 mmol). This free base diamine is added to a stirred solution of 5-bromo-2-fluorophenylisothiocyanate (prepared from 5-bromo-2-fluoroaniline, CAS #2924-09-6, catalog #18297, Matrix Scientific, PO Box 25067, Columbia, S.C. 29224) (0.464 g, 2.0 mole) in acetonitrile (20 mL). Cesium carbonate (2.6 g, 8.0 mmol) is added to the reaction mixture. The reaction mixture is then heated to 150° C. under microwave irradiation for 30 minutes. The reaction mixture is cooled to room temperature then diluted with water and extracted with chloroform. The organic layer is dried (MgSO4) and filtered. The filtrate is concentrated under reduced pressure to give a residue that is purified by silica gel chromatography (100% dichloromethane to 50:50 dichloromethane/90% dichloromethane and 10% methanol). Fractions containing product are combined and concentrated under reduced pressure to give (R)-5-bromo-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazole.

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

ORD record

ord-2e463ccb8ff648aeba2643d08123deb3

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580968B2