Sodium borohydride → HCID 21947345, compound

Temperature

10 °C

((11—N-phthalimidoundecyl)-ethoxyphosphinyl)methylphosphonic acid dimethyl ester (37.15 g, 78 mmol) was dissolved in a mixture of 2-propanol (165 mL) and water (26 mL). The mixture was cooled to about 10° C. in an ice bath and NaBH4 (11.11 g, 293 mmol, 3.8 eq.) was added slowly. The mixture was filtered and then cooled to below 5° C. in an ice bath. Acetic acid (70 mL) was then added slowly to the mixture. When the addition was complete the mixture was heated to 90° C. for 6 days. The mixture was then cooled to room temperature and the solvent removed. Residual water and acetic acid were removed from the residue azeotropically using ethyl acetate (200 mL), and then again using acetone two times (500 mL) and then again using toluene two times (500 mL). The resulting residue was free from acetic acid. This residue was partitioned between water (300 mL) and ethyl acetate (300 mL). The layers were separated and the organic layer was discarded. The aqueous layer was lyophilized to give a mixture of inorganic salts and ((11-aminoundecyl)-ethoxyphosphinyl)methylphosphonic acid. This solid was suspended in HCl (36%, 75 mL) and heated to 90° C. overnight. A clear solution was obtained. The mixture was cooled to room temperature and a solid precipitate formed. This solid was removed by centrifugation and found (by NMR) to contain no product. This solid was discarded. The supernatant was concentrated and again a solid appeared as a suspension in solution. HCl was removed from this suspension azeotropically using water (100 mL). After removal of HCl, an oily suspension was obtained. When additional water was added (100 mL), the product appeared as a white solid. This solid was collected by centrifugation. The solid was washed two times with acetone (70 mL) and dried in vacuum oven at 35° C. (recovery=9.98 g). A second crop was obtained by concentrating the supernatant and heating it with HCl (36%, 40 mL) for 2 hours. The solvent was removed to dryness and the mixture was suspended in water (20 mL), centrifuged to collect solid product, and the solid was washed with water (10 mL) and two times with acetone (20 mL) (recovery=2 g). 1H NMR (D2O) δ=2.3 (t, 2H), 1.6 (t, 2H), 1.4 (m, 2H), 1.2-1.0 (m, 18H). 31P NMR (D2O) δ=13.8, 42.6.

1. filtrationThe mixture was filtered
2. temperaturecooled to below 5° C. in an ice bath
3. additionAcetic acid (70 mL) was then added slowly to the mixture
4. additionWhen the addition
5. temperaturewas heated to 90° C. for 6 days
6. temperatureThe mixture was then cooled to room temperature
7. customthe solvent removed
8. customResidual water and acetic acid were removed from the residue azeotropically using ethyl acetate (200 mL)
9. customThis residue was partitioned between water (300 mL) and ethyl acetate (300 mL)
10. customThe layers were separated
11. customto give
12. temperatureheated to 90° C. overnight
13. customA clear solution was obtained
14. temperatureThe mixture was cooled to room temperature
15. customa solid precipitate formed
16. customThis solid was removed by centrifugation
17. concentrationThe supernatant was concentrated
18. customHCl was removed from this suspension azeotropically using water (100 mL)
19. customAfter removal of HCl
20. customan oily suspension was obtained
21. customThis solid was collected by centrifugation
22. washThe solid was washed two times with acetone (70 mL)
23. customdried in vacuum oven at 35° C. (recovery=9.98 g)
24. customA second crop was obtained
25. concentrationby concentrating the supernatant and
26. temperatureheating it with HCl (36%, 40 mL) for 2 hours
27. customThe solvent was removed to dryness
28. customto collect solid product
29. washthe solid was washed with water (10 mL) and two times with acetone (20 mL) (recovery=2 g)

ORD record

ord-72ab7985b33841eaa3cf60bff3599827

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07754200B2