Toluene → (R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanal

Temperature

0 °C

A solution of (2E)-3-cyclopentylacrylaldehyde (28, 654 mg, 5.0 mmol, 5.0 equiv), (2R)-2-(bis[3,5-bis(trifluoromethyl)phenyl][tert-butyl(dimethyl)silyl]oxymethyl)pyrrolidine ((R)-35, 64 mg, 0.10 mmol, 0.10 equiv) and 4-nitrobenzoic acid (17 mg, 0.10 mmol, 0.10 equiv) in anhydrous toluene (4.0 mL, 38 mmol) was stirred at rt for 10 min, then cooled to 0° C. before 4-bromo-1H-pyrazole (39, 148 mg, 1.0 mmol) was then added. The resulting reaction mixture was stirred at 0° C. for 22 h. When LCMS showed the reaction was deemed complete, the reaction mixture was concentrated under reduced pressure. The residue was directly purified by CombiFlash (SiO2) with 0-30% EtOAc/hexane gradient elution to give (3R)-3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropanal ((R)-40, 230.5 mg, 271.2 mg theoretical, 85% yield) as a pale yellow viscous oil. For (R)-40: C11H15BrN2O (MW, 271.15), LCMS (EI) m/e 271/273 (M++H).

1. additionwas then added
2. customThe resulting reaction mixture
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. customThe residue was directly purified by CombiFlash (SiO2) with 0-30% EtOAc/hexane gradient elution

ORD record

ord-5b578cb7ada64fb9afa7c9f403e5a1cd

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993582B2