Iodine → (3R)-3-(4-Bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile

To a stirred solution of (3R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanal ((R)-40, 230.5 mg, 0.85 mmol) in tetrahydrofuran (THF, 2.4 mL, 29 mmol) at room temperature was added a solution of 14.3 M of ammonium hydroxide (NH4OH) in water (2.4 mL), followed by iodine (I2, 237 mg, 0.935 mmol, 1.1 equiv). The resulting reaction mixture was stirred at room temperature for 30 min. When LCMS showed that the reaction was complete, the reaction mixture was quenched with 10% aqueous Na2S2O3 solution (15 mL) and extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine, dried over magnesium sulfate (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by Combiflash (SiO2) with 0-30% EtOAc/hexane gradient elution to give (3R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile ((R)-41, 180.7 mg, 227.9 mg theoretical, 79.3% yield) as a colorless viscous oil.

1. customThe resulting reaction mixture
2. customthe reaction mixture was quenched with 10% aqueous Na2S2O3 solution (15 mL)
3. extractionextracted with EtOAc (2×15 mL)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over magnesium sulfate (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by Combiflash (SiO2) with 0-30% EtOAc/hexane gradient elution

ORD record

ord-b32106b84b544333a713a05be839f063

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290506B2