Diisobutylaluminum hydride → (E)-3-(1-(4-fluorophenyl)cyclohexyl)prop-2-en-1-ol

To a solution of (E)-ethyl 3-(1-(4-fluorophenyl)cyclohexyl)acrylate (Intermediate I-7B, 1.5 g, 5.43 mmol) in toluene (30 mL) was added 2.5 M DIBAL-H in toluene (6.51 mL, 16.28 mmol) dropwise at room temperature, and the mixture was stirred at the same temperature for 5.5 hrs. The reaction was quenched by dropwise addition of methanol (1.34 mL) and stirring was continued for a few minutes. Then water (1.96 mL) was added dropwise and the mixture was stirred overnight at room temperature. The resulting mixture was filtered through CELITE® and evaporated to give an oily residue. It was purified by Combiflash (silica gel, 40 g) eluting with 5:95 followed by 1:9 and 2:8 ethyl acetate-hexane to give the desired (E)-3-(1-(4-fluorophenyl)cyclohexyl)prop-2-en-1-ol (964 mg, 76% yield) along with 232 mg of the unreacted starting material. 1H NMR (400 MHz, CDCl3) δ ppm 7.30 (2H, dd, J=8.91, 5.39 Hz), 7.00 (2H, t, J=8.80 Hz), 5.70 (1H, d, J=15.85 Hz), 5.43 (1H, dt, J=15.74, 5.94, 5.83 Hz), 4.11 (2H, dd, J=5.72, 1.32 Hz), 1.97-2.05 (2H, m), 1.78-1.86 (2H, m), 1.53-1.63 (3H, m), 1.40-1.52 (5H, m).

1. customThe reaction was quenched by dropwise addition of methanol (1.34 mL)
2. stirringstirring
3. waitwas continued for a few minutes
4. additionThen water (1.96 mL) was added dropwise
5. stirringthe mixture was stirred overnight at room temperature
6. filtrationThe resulting mixture was filtered through CELITE®
7. customevaporated
8. customto give an oily residue
9. customIt was purified by Combiflash (silica gel, 40 g)
10. washeluting with 5:95

ORD record

ord-026eb043158e499caf1f51504a9c237e

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216972B2