Aluminium lithium hydride → HCID 90408285, compound

To a solution of methyl 2-((1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)methyl)cyclopropanecarboxylate (110 mg, 0.280 mmol) in THF (1 mL) at 0° C. was added LAH (0.280 ml, 0.280 mmol) dropwise. The reaction was stirred at rt for 3 h, added CELITE® (200 mg), cooled to −78° C., and then quenched with sat′d aqueous NH4Cl (0.5 mL). The mixture was stirred at rt for 30 min, added MgSO4 (200 mg), and stirred at rt for another 1 h. The mixture was filtered. The solid was washed with DCM. The combined filtrates were concentrated in vacuo and the residue was purified by flash chromatography on SiO2 (0 to 30% EtOAc:hexanes) to afford the title compound (101 mg, 99% yield) as a clear oil. LCMS, [M+NH4]+=382.2. 1H NMR (500 MHz, CDCl3) δ 7.34-7.24 (m, 3H), 7.16-7.10 (m, 2H), 7.09-7.05 (m, 1H), 7.00-6.96 (m, 2H), 6.85-6.81 (m, 1H), 3.87 (s, 2H), 3.55 (dd, J=11.0, 6.6 Hz, 1H), 3.41 (dd, J=11.0, 7.2 Hz, 1H), 2.05-1.99 (m, 4H), 1.76-1.69 (m, 4H), 1.14 (dd, J=6.9, 4.7 Hz, 2H), 0.84-0.76 (m, 1H), 0.62-0.54 (m, 1H), 0.45-0.39 (m, 1H), 0.28 (dt, J=8.3, 4.8 Hz, 1H).

1. additionadded CELITE® (200 mg)
2. temperaturecooled to −78° C.
3. customquenched with sat′d aqueous NH4Cl (0.5 mL)
4. stirringThe mixture was stirred at rt for 30 min
5. additionadded MgSO4 (200 mg)
6. stirringstirred at rt for another 1 h
7. filtrationThe mixture was filtered
8. washThe solid was washed with DCM
9. concentrationThe combined filtrates were concentrated in vacuo
10. customthe residue was purified by flash chromatography on SiO2 (0 to 30% EtOAc:hexanes)

ORD record

ord-f961027040b14342bafb6a791a0ff973

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962660B2