Dimethyl Sulfoxide → 3-[2-(Tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridine-2-carbaldehyde

Temperature

-78 °C

To a three-necked round flask containing dry DCM (500 mL) cooled down to −78° C. under an atmosphere of N2 was added oxalyl chloride (20.0 mL, 157 mmol) followed by a careful dropwise addition of DMSO (24.5 g, 315 mmol). To the cold reaction mixture was {3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}methanol (from Example 19, Step 1; 21.0 g, 82.9 mmol) in DCM (25 mL) carefully added, the temperature never exceeded −65° C. After the addition, the reaction mixture was stirred at −78° C. for one hour after which time TEA (50.2 g, 497 mmol) was added and the mixture was stirred another 30 minutes at ambient temperature. To the mixture was added ice water (400 mL) and the organic phase was washed H2O, brine, dried (MgSO4), the brown organic phase was filtered through a pad (60 mm×40 mm) of silica and finally the solvent was removed under reduced pressure to give a brown oil. The hydrated aldehyde was dissolved in toluene (150 mL) and heated for 3 h under Dean-Stark conditions to give 19.9 g (95%) of the title compound as a black oil. HRMS m/z calcd for C13H17NO4 (M)+ 251.1158. found 251.1153.

1. customTo the cold reaction mixture
2. additioncarefully added
3. customthe temperature never exceeded −65° C
4. additionAfter the addition
5. additionwas added
6. washthe organic phase was washed H2O, brine
7. dry with materialdried (MgSO4)
8. filtrationthe brown organic phase was filtered through a pad (60 mm×40 mm) of silica
9. customfinally the solvent was removed under reduced pressure
10. customto give a brown oil
11. temperatureheated for 3 h under Dean-Stark conditions

ORD record

ord-ae61a111296240f9b52e6a21cf508ae5

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07226925B2