5-(CHLOROMETHYL)-3-ETHYL-1,2,4-OXADIAZOLE synthesis

Yield:50737-34-3 14%

Reaction Conditions:

for 1.16667 h;Heating / reflux;

Steps:

B.62.1

To crude N-hydroxypropanimidamide (80 g, 0.91 mol), obtained from propionitrile and hydroxylamine (Moloney, G. P.; Martin, G. R.; Mathews, N.; Maclennan, S.; Dodsworth, S.; Sang, P. Y.; Knight, C.; Maxwell, M.; Glen, R. C. J. Chem. Soc Perkin I 1999, 19, 2725), was added chloroacetyl chloride (411 g, 3.64 mol, 4 equiv). After the initial exothermic reaction subsided, the mixture was refluxed for 70 min. The reaction mixture was cooled to room temperature, and the excess chloroacetyl chloride evaporated. The residue was dissolved in ethyl acetate, diluted with hexanes, and filtered to remove dark solid impurities. The filtrate was evaporated, treated with ice-cold aqueous NaHCO₃, and extracted with ethyl acetate (2×150 mL). The extract was dried over Na₂SO₄, filtered, and the solvent evaporated, affording 76.25 g of an oil. This was subjected to fractional distillation, affording 16.5 g (14%) of the title product (bp 36° C./0.05 Torr; lit bp 88° C./35 Torr: Hagerty, J. D. U.S. Pat. No. 3,956,498, May 11, 1976). ¹H NMR (CDCl₃) d 1.31 (t, J=7 Hz, 3H), 2.75 (q, J=7 Hz, 2H), 4.64 (s, 2H). LC-MS (APCI) calcd for C₅H₇ClN₂O: 146.02; found (M+H⁺): 147.0 m/z.

References:

US2005/176701,2005,A1 Location in patent:Page/Page column 150-151