Methyl iodide → (3-Amino-1-ethyl-propyl)-methyl-phosphinic acid

Participants

Reaction Steps

A mixture of 4,53 g (30 mmol) of P-(5-aminopent-3-yl)phosphonous acid and 24.21 g (150 mmol) of hexamethyldisilazane is refluxed under argon while stirring for 16 hours. To the resulting solution 15 ml of diethylene glycol dimethyl ether are added and boiling is continued for additional 2 hours. The reaction mixture is cooled to 100° and 19.38 g (150 mmol) of N-ethyl-N,N-diisopropyl-amine are added over a period of 20 minutes. After cooling to 25°, 21.29 g (15 mmol) of methyliodide are added over a period of 20 minutes, the reaction temperature being kept at 25° with external cooling. The reaction mixture is stirred for 4 days, then cooled to 10°. The white precipitate is filtered off. The filtrate is evaporated under reduced pressure, and the residue diluted with 100 ml of cold dichloromethane and extracted three times with 50 ml each of 2N hydrochloric acid. The extracts are combined, evaporated to dryness and co-evaporated 2 additional times with 50 ml each of water to give a colourless oil. This oil is dissolved in 50 ml of methanol, 300 ml of propylene oxide are added and the mixture is kept at 4° overnight and then evaporated under reduced pressure. The crude product is purified by chromatography on 150 g of Opti-Up® C12 with water as eluent. The fractions containing the desired product are combined and evaporated under reduced pressure. The solid residue is dried under reduced pressure yielding P-(5-aminopent-3-yl)-P-methyl-phosphinic acid ×0.52 H2O (hygroscopic).

Provenance & Evidence