Methyl iodide → 4-Methyloxane-4-carbonitrile

Temperature

0 °C

To a solution of tetrahydro-2H-pyran-4-carbonitrile (2 g, 18.00 mmol) in THF (10 mL) at 0-5° C. was slowly added LHMDS (21.59 mL, 21.59 mmol). The mixture was stirred for 1.5 hr 0° C. Iodomethane (3.37 mL, 54.0 mmol) was added slowly and stirring was continued for 30 min at ˜0° C. and ˜2 hr at ambient temperature. The mixture was cooled to 0° C. and carefully diluted with 1N aqueous HCl (30 mL) and EtOAc (5 mL) and concentrated. The resulting residue was taken up in diethylether and the separated organic layer was washed with brine, dried over Na2SO4, filtered off and concentrated in vacuo providing crude 4-methyltetrahydro-2H-pyran-4-carbonitrile as an orange oil, which was directly used in the next reaction without further purification. Yield: 1.8 g. LCMS (m/z): 126.1 [M+H]+; Retention time=0.44 min.

1. customat 0-5° C.
2. stirringstirring
3. waitwas continued for 30 min at ˜0° C. and ˜2 hr at ambient temperature
4. temperatureThe mixture was cooled to 0° C.
5. concentrationconcentrated
6. washthe separated organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered off
9. concentrationconcentrated in vacuo

ORD record

ord-a88536a38c1a4a938e964e6bed3304a8

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778951B2