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. Purify 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
10. customPurify the residue by chromatography on silica gel eluting sequentially with hexane/EtOAc (1:0 to 4:1 gradient)

ORD record

ord-58e513b40a0b46ef9536849d5a087074

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580780B2