초록 ▼

A scalable process for purification of phosphorodiamidite includes steps of solubilizing a crude phosphorodiamidite in an apolar organic solvent, contacting the non-polar organic solvent with a polar phase comprising a polar organic solvent to remove impurities from the solubilized phosphorodiamidit

A scalable process for purification of phosphorodiamidite includes steps of solubilizing a crude phosphorodiamidite in an apolar organic solvent, contacting the non-polar organic solvent with a polar phase comprising a polar organic solvent to remove impurities from the solubilized phosphorodiamidite, and removing the non-polar organic solvent from the phosphorodiamidite.

대표청구항 ▼

We claim: 1. A process of producing a purified phosphorodiamidite, said process comprising the steps of: a. dissolving a crude phosphorodiamidite containing at least one impurity in an apolar phase; and b. contacting the apolar phase with a polar phase comprising a polar organic solvent, whereby at

We claim: 1. A process of producing a purified phosphorodiamidite, said process comprising the steps of: a. dissolving a crude phosphorodiamidite containing at least one impurity in an apolar phase; and b. contacting the apolar phase with a polar phase comprising a polar organic solvent, whereby at least a portion of the impurity is transferred into the polar phase and the purified phosphorodiamidite is produced in the apolar phase; wherein said phosphorodiamidite is represented by formula I: G1 is OR1; R1 is cyanoethyl; each G2 is independently--NR2R3, and R2 and R3 are independently alkyl, substituted alkyl, alkenyl, substituted alkenyl. 2. The process of claim 1, wherein the phosphorodiamidite is the most lipophilic solute in the apolar phase of step (a). 3. The process of claim 1, wherein the apolar phase comprises a liquid hydrocarbon. 4. The process of claim 3, wherein the apolar phase comprises alkanes. 5. The process of claim 1, wherein the polar phase comprises acetonitrile, N,N-dimethylformamide (DMF), ethylene glycol, glycerol, acetamide, ethylene diamine, N,N,-dimethylacetamide, N-methylacetamide, N-methylformamide, dimethylsulfoxide, ethanolamine, diethanolamine, triethanolamine, caprolactam, 3-hydroxypropiononitrile, hexamethylphosphoric triamide, dimethylurea, tetramethylurea, 2-pyrrolidinone, N-methylpyrrolidinone or 2-imidazolidone. 6. The process of claim 5, wherein the apolar phase comprises hexanes. 7. The process of claim 6, wherein the polar phase comprises acetonitrile. 8. The process of claim 7, wherein the polar phase further comprises water. 9. The process of claim 8, wherein the polar phase comprises a mixture of acetonitrile and water in the range of about 50:50 to about 90:5 (v/v). 10. The process of claim 9, wherein the polar phase comprises a mixture of acetonitrile and water in the range of about 50:50 to about 80:20 (v/v). 11. The process of claim 3, wherein the apolar phase comprises toluene. 12. The process of claim 11, wherein the polar phase comprises acetonitrile, N,N-dimethylformamide (DMF), ethylene glycol, glycerol, acetamide, ethylene diamine, N,N,-dimethylacetamide, N-methylacetamide, N-methylformamide, dimethylsulfoxide, ethanolamine, diethanolamine, triethanolamine, caprolactam, 3-hydroxypropiononitrile, hexamethylphosphoric triamide, dimethylurea, tetramethylurea, 2-pyrrolidinone, N-methylpyrrolidinone or 2-imidazolidone. 13. The process of claim 1, further comprising at least one additional step of contacting a polar phase with the apolar phase. 14. The process of claim 1, wherein the apolar phase and the polar phase are contacted at room temperature. 15. The process of claim 1, wherein the apolar phase and the polar phase are contacted with agitation. 16. The process of claim 1, further comprising the following step (c): (c) separating the apolar phase from the polar phase. 17. The process of claim 1, further comprising the following steps (c) and (d): (c) separating the apolar phase from the polar phase; and (d) removing the apolar organic solvent from the purified phosphorodiamidite. 18. The process of claim 1, wherein the phosphorodiamidite is the most hydrophobic compound in the apolar phase. 19. A process of purifying a phosphorodiamidite compound of formula Va: said process comprising the steps of: a. dissolving the phosphorodiamidite of formula Va and at least one impurity in an apolar organic solvent to form an apolar phase; and b. contacting the apolar phase with a polar phase comprising a polar organic solvent, whereby at least a portion of the impurity partitions into the polar phase, thereby producing the purified phosphorodiamidite in the apolar phase. 20. The process of claim 19, wherein the apolar phase comprises hexanes. 21. The process of claim 19, wherein the polar phase comprises acetonitrile. 22. The process of claim 21, wherein the polar phase further comprises water. 23. The process of claim 22, wherein the polar phase comprises acetonitrile and water in a ratio within the range of about 50:50 to about 95:5 (v/v). 24. The process of claim 23, wherein the polar phase comprises acetonitrile and water in a ratio within the range of about 50:50 to about 80:20 (v/v). 25. The process of claim 19, wherein the proccss is carried out at about room temperature. 26. The process of claim 19, further comprising at least one additional step of contacting a polar phase with the apolar phase. 27. The process of claim 19, wherein the apolar phase and the polar phase are contacted at room temperature. 28. The process of claim 19, wherein the apolar phase and the polar phase are contacted with agitation. 29. The process of claim 19, further comprising the following step c.: c. separating the apolar phase from the polar phase. 30. The process of claim 19, further comprising the following steps c. and d.: c. separating the apolar phase from the polar phase; and d. removing the apolar organic solvent from the purified phosphorodiamidite. 31. The process of claim 19, wherein the phosphorodiamidite of formula Va is the most lipophilic compound in the apolar phase of step a. 32. The process of claim 19, wherein the phosphorodiamidite is the most lipophilic compound in the apolar phase of step a. 33. A process of making a purified phosphorodiamidite, said process comprising a. obtaining a crude phosphorodiamidite composition comprising phosphorodiamidite and at least one impurity; b. dissolving said crude phosphorodiamidite composition in an apolar organic solvent to form an apolar phase; c. contacting said apolar phase with a polar phase comprising a polar organic solvent, whereby at least a portion of said impurity partitions into the polar phase; and d. separating the apolar phase from the polar phase, whereby a purified phosphorodiamidite is obtained in the apolar phase wherein said phosphorodiamidite is represented by formula I: G1 is OR1; R1 is cyanoethyl; each G2 is independently--NR2R3, and R2 and R3 are independently alkyl, substituted alkyl, alkenyl, substituted alkenyl. 34. The process of claim 1, wherein said apolar phase is hexane and said polar phase is a mixture of acetonitrile and water.