Acetic Acid → 3-chloro-2(R)-hydroxy-propyl(cyclohexylmethyl)phosphinic acid ethyl ester

20.0 g of cyclohexylmethylphosphinic acid ethyl ester are dissolved in 150 ml of tetrahydrofuran, and at 0° 11.0 g of triethylamine and then, dropwise, 12.0 g of trimethylchlorosilane are added, a white precipitate being formed. The resulting suspension is stirred at room temperature for 24 hours and then filtered under argon. The filtrate is concentrated by evaporation under reduced pressure. 10.9 g of (R)-epichlorohydrin and 2.0 g of anhydrous zinc chloride are added to the residue. When the exothermic reaction has died away, the mixture is heated under reflux at 60° for a further 24 hours. The reaction mixture is allowed to cool to room temperature, diluted with dichloromethane and washed with water. The organic phase is separated off, dried over sodium sulfate and concentrated by evaporation. The residue is dissolved in dichloromethane and washed with water. Drying over sodium sulfate and concentration by evaporation yield an oil. The oil is taken up in % methanolic acetic acid, left to stand at room temperature for 24 hours and then concentrated by evaporation. The residue is purified by chromatography on silica gel, yielding 3-chloro-2(R)-hydroxy-propyl(cyclohexylmethyl)phosphinic acid ethyl ester; 1H-NMR spectrum (in CDCl3): δ=4.47 (1H,d), 4.21-4.02 (3H,m), 3.6 (2H,m), 2.11-1.54 (9H,m), 1.38-0.97 (9H,m).

1. customa white precipitate being formed
2. filtrationfiltered under argon
3. concentrationThe filtrate is concentrated by evaporation under reduced pressure
4. addition10.9 g of (R)-epichlorohydrin and 2.0 g of anhydrous zinc chloride are added to the residue
5. customWhen the exothermic reaction
6. temperaturethe mixture is heated
7. temperatureunder reflux at 60° for a further 24 hours
8. temperatureto cool to room temperature
9. washwashed with water
10. customThe organic phase is separated off
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated by evaporation
13. dissolutionThe residue is dissolved in dichloromethane
14. washwashed with water
15. dry with materialDrying over sodium sulfate and concentration by evaporation
16. customyield an oil
17. waitleft
18. waitto stand at room temperature for 24 hours
19. concentrationconcentrated by evaporation
20. customThe residue is purified by chromatography on silica gel

ORD record

ord-72c1f35cd3824eaa8d5a0e1110b02c00

Source dataset

uspto-grants-1994_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05376684