Tetrahydrofuran → 1-Fluoro-2-amino-5-ethoxy-3-pentene

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen, 3-ethoxy-1-propen-1-yl-magnesium bromide is prepared from 8.25 g of 1-bromo-3-ethoxy-1-propene (50 mmoles) prepared as in Step B above, 12.15 g of magnesium turnings (500 mmoles) and 50 ml of dry tetrahydrofuran. After 4 hours the Grignard solution (yield according to titration: 80%) is transferred into another flask via a syringe, cooled to -30° C. and fluoroacetonitrile (2.36 g, 40 mmoles) in tetrahydrofuran (30 ml) is added dropwise during 15 mins. After 15 additional minutes at -30° C., a solution/suspension of sodium borohydride (1.52 g, 40 mmoles) in methanol (100 ml) and water (2 ml) cooled to -50° C. is poured into the reaction mixture previously cooled to -50° C. The temperature rises up to -30° C., and after stirring for 20 mins. at -20° C., the mixture is allowed to warm up to 0° C. during 1 hour. After acidifying with 6 N hydrochloric acid and evaporation, the residue is extracted twice with diethyl ether to remove by-products, made alkaline with 4 N sodium hydroxide and extracted twice with diethyl ether. Evaporation of the solvent affords crude 1-fluoro-2-amino-5-ethoxy-3-pentene (cis/trans) as a colored oil (1.0 g, 17%, based on the Grignard).

Provenance & Evidence