Diisobutylaluminum hydride → HCID 90408708, compound

Temperature

-78 °C

To a −78° C. solution of 2-(1-(3-fluoro-5-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl) acetaldehyde (424 mg, 1.22 mmol) in DCM (5 mL) under N2 was added DIBAL-H (1.34 mL of a 1.0 M solution in DCM, 1.34 mmol) dropwise. The reaction mixture was stirred at −78° C. for 2 h; CELITE® (500 mg) was then added and the reaction was quenched with sat. aq. NH4Cl (0.5 mL). The mixture was stirred at rt for 30 min, MgSO4 (500 mg) was added, and the mixture was stirred at rt for 30 min. The mixture was filtered and the residual solid was washed with DCM (3×). The combined filtrates were concentrated in vacuo. The crude oil was purified by flash chromatography (SiO2) using a gradient of 0% to 50% EtOAc/hexane (10 min) to give the title compound (350 mg, 1.00 mmol, 82% yield) as a clear oil. 1H NMR (CDCl3) δ: 6.85 (t, J=1.7 Hz, 1H), 6.73 (ddd, J=10.1, 2.3, 1.5 Hz, 1H), 6.66 (dt, J=10.6, 2.3 Hz, 1H), 5.38 (t, J=3.1 Hz, 1H), 3.94-3.81 (m, 3H), 3.70 (td, J=7.2, 4.1 Hz, 2H), 3.60 (dtd, J=11.3, 4.0, 1.2 Hz, 1H), 2.04-1.92 (m, 5H), 1.90-1.77 (m, 2H), 1.76-1.52 (m, 8H), 1.45 (t, J=7.3 Hz, 2H); 19F NMR (CDCl3) δ: −112.1 (s).

1. additionCELITE® (500 mg) was then added
2. customthe reaction was quenched with sat. aq. NH4Cl (0.5 mL)
3. stirringThe mixture was stirred at rt for 30 min
4. additionMgSO4 (500 mg) was added
5. stirringthe mixture was stirred at rt for 30 min
6. filtrationThe mixture was filtered
7. washthe residual solid was washed with DCM (3×)
8. concentrationThe combined filtrates were concentrated in vacuo
9. customThe crude oil was purified by flash chromatography (SiO2)
10. customa gradient of 0% to 50% EtOAc/hexane (10 min)

ORD record

ord-dbb0e9307d6141509c754aa60651371c

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962660B2