Methyl iodide → 1-aminopentan-3-yl(methyl)phosphinic acid

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).

1. temperatureis refluxed under argon
2. waitboiling is continued for additional 2 hours
3. temperatureThe reaction mixture is cooled to 100°
4. temperatureAfter cooling to 25°
5. custombeing kept at 25° with external cooling
6. stirringThe reaction mixture is stirred for 4 days
7. temperaturecooled to 10°
8. filtrationThe white precipitate is filtered off
9. customThe filtrate is evaporated under reduced pressure
10. additionthe residue diluted with 100 ml of cold dichloromethane
11. extractionextracted three times with 50 ml each of 2N hydrochloric acid
12. customevaporated to dryness
13. customto give a colourless oil
14. waitthe mixture is kept at 4° overnight
15. customevaporated under reduced pressure
16. customThe crude product is purified by chromatography on 150 g of Opti-Up® C12 with water as eluent
17. additionThe fractions containing the desired product
18. customevaporated under reduced pressure
19. customThe solid residue is dried under reduced pressure

ORD record

ord-c4dbbd59bb7a4b96a3ac7e5625fdb772

Source dataset

uspto-grants-1996_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05567840