Tetrahydrofuran → 2-Cyclohexylmethyl-benzothiazole-6-carbonitrile

Temperature

80 °C

Place 2-bromo-benzothiazole-6-carbonitrile (0.2 g, 0.96 mmol), anhydrous THF (3 mL), 1-methyl-2-pyrrolidinone (3 mL), tetrabutylammonium iodide (1.1 g, 2.89 mmol), tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.09 mmol) and [1,1′-bis(diphenylphosphino)ferrocine]dichloropalladium (II) (11 mg, 0.09 mmol) in a flask. Add 0.5M cyclohexylmethylzinc bromide in THF (3.8 mL, 1.92 mmol) to the mixture, degas 3 times by partially evacuating the atmosphere and flushing with nitrogen and stir the reaction mixture at 80° C. for 2 h. Cool the reaction mixture to room temperature, dilute with EtOAc (10 mL) and wash with brine (10 mL). Dry the organic layer over anhydrous Na2SO4, filter and concentrate in vacuo. Purity the residue by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:0 to 4:1 gradient) to obtain the desired intermediate as a yellow solid (140 mg, 57%). GC-MS m/z: 256 (M+).

1. customdegas 3 times
2. customby partially evacuating the atmosphere
3. customflushing with nitrogen
4. temperatureCool the reaction mixture to room temperature
5. additiondilute with EtOAc (10 mL)
6. washwash with brine (10 mL)
7. dry with materialDry the organic layer over anhydrous Na2SO4
8. filtrationfilter
9. concentrationconcentrate in vacuo

ORD record

ord-a3e65b8c4beb4fda9756db4a3b5ff877

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022062B2