Ethylene Glycol → 2-(1-(3-Hydroxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetic acid

Temperature

165 °C

A mixture of 4-(iodomethyl)-1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octane (1.5 g, 3.50 mmol) and NaCN (0.687 g, 14.01 mmol) in DMF (8 mL) was stirred at 80° C. for 18 h. The reaction was diluted with EtOAc (10 mL), washed with water (3×10 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo to give 2-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)acetonitrile (1.15 g, 3.50 mmol, 100% yield) as light brown oil. The above nitrile (1.15 g, 3.50 mmol) was taken up in ethylene glycol (20 mL) and treated with 40% KOH (5.00 mL, 35.0 mmol). The reaction was stirred at 165° C. for 18 h and concentrated in vacuo. The residue was dissolved in water (15 mL), acidified to pH 2 with 1 N aqueous HCl, and extracted with EtOAc (5×5 mL). The combined extracts were washed with brine, dried with MgSO4, filtered, and concentrated in vacuo to afford the title compound (0.91 g, 99% yield) as a light brown solid. LCMS, [M−H]+=261.3.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in water (15 mL)
3. extractionextracted with EtOAc (5×5 mL)
4. washThe combined extracts were washed with brine
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-c6d12d99efcf4d3d9cfa0bd059fc32f7

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08962660B2