1-Chloro-2-(chloromethoxy)ethane → HCID 67439994, compound

Temperature

25 °C

A solution of tetrahydro-2H-pyran-4-carbonitrile (3.80 g, 34.2 mmol) in tetrahydrofuran (10 ml) was added dropwise over 5 min to a cold (−78° C.) solution of lithium diisopropylamine (37.5 mmol) in tetrahydrofuran (50 ml). After 30 min, a solution of 2-chloroethyl chloromethyl ether (5.00 g, 38.7 mmol) in tetrahydrofuran (10 ml) was added dropwise over 5 min and the mixture stirred for 30 min. The cooling bath was then removed and the solution was allowed to warm up to 25° C. then stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic fraction was dried over anhydrous magnesium sulfate and concentrated. Filtration of the residue on silica gel (elution toluene-ethyl acetate 8:2) followed by distillation in vacuo gave 6.33 g (91% yield) of the title nitrile as a clear oil: bp 90-100° C./0.2 torr (bulb to bulb distillation, air bath temperature). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.74 (2H, m, CH2), 1.92 (2H, m, CH2), 3.58 (2H, s, CH2), 3.67 (2H, t, J=5.6 Hz, CH2), 3.74 (2H, dt, J=2.3 Hz and J=12.4 Hz, CH2), 3.83 (2H, t, J=5.6 Hz, CH2), 4.0 (2H, m, OCH2).

1. customThe cooling bath was then removed
2. stirringthen stirred for 1.5 h
3. customThe reaction mixture was quenched with saturated ammonium chloride
4. extractionextracted with ethyl acetate
5. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
6. concentrationconcentrated
7. filtrationFiltration of the residue on silica gel (elution toluene-ethyl acetate 8:2)
8. distillationfollowed by distillation in vacuo

ORD record

ord-29414dd1b0764d94a65669f6e1f57656

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08039458B2