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A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar

A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar phase to extract impurity into the apolar phase, separating the first apolar phase from the polar phase, adding a second aliquot of water to the polar phase, and contacting the polar phase with a second apolar phase, whereby the phosphoramidite partitions into the second apolar phase.

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We claim: 1. A process of purifying a phosphitylated compound of formula I: wherein G1 is O or S; G2 is a protecting group; G3 is an amine; Z is Z1 or Z2; Z1 has the formula: Z2 has the formula: Y is O or S; R'2 is protected OH,; H, HO, OR5, NR 5R6, F, Cl, Br, alkyl, substituted alkyl, heteroc

We claim: 1. A process of purifying a phosphitylated compound of formula I: wherein G1 is O or S; G2 is a protecting group; G3 is an amine; Z is Z1 or Z2; Z1 has the formula: Z2 has the formula: Y is O or S; R'2 is protected OH,; H, HO, OR5, NR 5R6, F, Cl, Br, alkyl, substituted alkyl, heterocyclyoalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aralkyl, substituted aralkyl, heterocycloaralkyl, substituted heterocycloaralkyl; or R'2 and R'4 together form a bridge; each of R5 and R6 is independently alkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hetaryl, substituted hetaryl, hetarylalkyl, substituted hetarylalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkanoyl, substituted alkanoyl, trialkylsilyl or substituted trialkylsilyl; or when R5 and R6 are on the same nitrogen, R5 and R6 may be taken together with the nitrogen to which they are bound to form a heterocyclyl ring or a substituted heterocyclyl ring R'4 is H or together with R'2 forms a bridge; m is an integer of 0 or 1, Bx is a heterocycle and G4 is a hydroxy protecting group; the process comprising: (a) providing the compound of formula I in a polar phase comprising a polar organic solvent and at least one impurity; (b) adding a basic compound and a first portion of water to the polar phase; (c) contacting the polar phase with a first apolar organic phase; (d) separating the first apolar organic phase from the polar phase; (e) adding a second portion of water to the polar phase and contacting the polar phase with a second apolar organic phase, the polar phase and the second apolar phase being contacted for a time sufficient for the compound of formula I to partition into the second apolar organic phase; and (f) separating the second apolar phase from the polar phase. 2. The process of claim 1, wherein step (e) comprises substeps carried out in order: (1) adding the second portion of water to the polar phase; and (2) contacting the polar phase with a second apolar organic phase. 3. The process of claim 2, wherein the second apolar phase comprises toluene. 4. The process of claim 2, wherein the polar phase comprises dimethylformamide. 5. The process of claim 1, wherein the step (e) is carried out in the order: (1) contacting the polar phase with a second apolar organic phase; and (2) adding the second portion of water to the polar phase. 6. The process of claim 5, wherein the second apolar phase comprises isopropyl ether or t-butyl methyl ether. 7. The process of claim 5, wherein the polar phase comprises acetonitrile. 8. The process according to claim 1, wherein Bx is a nucleobase. 9. The process according to claim 1, wherein the basic compound in step (b) is an amine. 10. The process according to claim 1, wherein the basic compound in step (b) is a tertiary amine. 11. The process according to claim 1, wherein the basic compound in step (b) is triethyl amine. 12. The process according to claim 1, wherein G3 is NR'R", wherein R' and R" are independently H or an organic moiety, or are taken together with the nitrogen to which they are attached to form a saturated or unsaturated heterocyclyl ring. 13. The process according to claim 12, wherein R' and R" are independently H, alkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hetaryl, substituted hetaryl, hetarylalkyl, substituted hetarylalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkanoyl, substituted alkanoyl, trialkylsilyl or substituted trialkylsilyl; or R' and R" are taken together with the nitrogen to which they are attached to form a 4-8-membered, saturated heterocyclyl group, which is optionally further substituted; or R' and R" are taken together with the nitrogen to which they are attached to form a 4-8-membered, unsaturated heterocyclyl group, which is optionally further substituted. 14. The process according to claim 1, wherein G2 is substituted alkyl. 15. The process according to claim 14, wherein G2 is substituted ethyl. 16. The process according to claim 15, wherein G2 is cyanoethyl. 17. The process according to claim 1, wherein G4 is dimethoxytrityl (DMT). 18. The process according to claim 1, wherein G1 is O. 19. The process according to claim 1, wherein Z is Z1 . 20. The process according to claim 19, wherein m is 1. 21. The process according to claim 1, wherein Z is Z2 . 22. The process according to claim 21, wherein m is 1. 23. The process according to claim 1, wherein Z is Z1 and R'2 and R'4 together form a bridge of subformula R'2--O(CH2)r--R'4, wherein r is 1 or 2, or R'2--CH2OCH2--R'4. 24. The process according to claim 23, wherein m is 1. 25. The process according to claim 23, wherein Z is Z2 and R'2 and R'4 together form a bridge of subformula R'2--O(CH2)r--R'4, wherein r is 1 or 2, or R'2--CH2OCH2--R'4. 26. A process of purifying a phosphitylated compound of formula I: wherein Bx is a heterocycle; Y is O or S; R'2 is protected OH, H, OH, OR5, NR 5R6, F, Cl, Br, alkyl, substituted alkyl, heterocyclyoalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aralkyl, substituted aralkyl, heterocycloaralkyl, substituted heterocycloaralkyl; or R'2 and R'4 together form a bridge; each of R5 and R6 is independently alkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hetaryl, substituted hetaryl, hetarylalkyl, substituted hetarylalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkanoyl, substituted alkanoyl, trialkylsilyl or substituted trialkylsilyl; or when R5 and R6 are on the same nitrogen, R5 and R6 may be taken together with the nitrogen to which they are bound to form a heterocyclyl ring or a substituted heterocyclyl ring and R'4 is H; or R'2 and R'4 together form a bridge; G1 is O or S; G2 is a protecting group; G3 is an amine; and G4 is a protecting group; the process comprising: (a) providing the compound of formula I in a polar phase comprising a polar organic solvent and at least one impurity; (b) adding a basic compound and water to the polar phase; (c) contacting the polar phase with a first apolar organic phase; (d) separating the first apolar organic phase from the polar phase; (e) adding a second portion of water to the polar phase and contacting the polar phase with a second apolar organic phase, the polar phase and the second apolar phase being contacted for a time sufficient for the compound of formula I to partition into the second apolar organic phase; and (f) separating the second apolar phase from the polar phase. 27. The process of claim 26, wherein step (e) comprises, in order, substeps: (1) adding the second portion of water to the polar phase; and (2) contacting the polar phase with a second apolar organic phase. 28. The process of claim 27, wherein polar phase comprises dimethylformamide. 29. The process of claim 27, wherein the second apolar organic phase comprises toluene. 30. The process of claim 26, wherein the step (e) comprises, in order, substeps: (1) contacting the polar phase with a second apolar organic phase; and (2) adding the second portion of water to the polar phase. 31. The process of claim 30, wherein the polar phase comprises acetonitrile. 32. The process of claim 30, wherein the second apolar organic phase comprises isopropyl ether or t-butyl methyl ether. 33. The process according to claim 26, wherein Bx is a nucleobase. 34. The process according to claim 26, wherein R'2 is OH, protected OH or a 2'-substituent, and R'2 is in the ribo-conformation. 35. The process according to claim 26, wherein the basic compound in step (b) is an amine. 36. The process according to claim 26, wherein the basic compound in step (b) is a tertiary amine. 37. The process according to claim 26, wherein the basic compound in step (b) is triethyl amine. 38. The process according to claim 26, wherein G3 is NR'R", wherein R' and R" are independently H or an organic radical, or are taken together with the nitrogen to which they are attached to form a saturated or unsaturated heterocyclyl ring. 39. The process according to claim 38, wherein R' and R" are independently H, alkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hetaryl, substituted hetaryl, hetarylalkyl, substituted hetarylalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkanoyl, substituted alkanoyl, trialkylsilyl or substituted trialkylsilyl; or R' and R" are taken together with the nitrogen to which they are attached to form a 4-8-membered, saturated heterocyclyl group, which is optionally further substituted; or R' and R" are taken together with the nitrogen to which they are attached to form a 4-8-membered, unsaturated heterocyclyl group, which is optionally thither substituted. 40. The process according to claim 26, wherein G2 is substituted alkyl. 41. The process according to claim 40, wherein G2 is substituted ethyl. 42. The process according to claim 41, wherein G2 is cyanoethyl. 43. The process according to claim 26, wherein G4 is DMT. 44. The process according to claim 26, wherein G1 is O. 45. A process of purifying a phosphitylated compound of formula I: wherein G4 is a protecting group; Bx is a nucleobase; R' and R" each independently represent a substituted-or unsubstituted hydrocarbyl radical having 1 to 10 carbon atoms, or taken together R' and R", together with the nitrogen to which they are attached, form a nitrogen-containing heterocyclyl ring, which optionally contains one or two additional hetero atoms, said nitrogen-containing heterocyclyl ring being saturated or unsaturated; R'2 is protected OH, H, OH, OR5, NR 5R6, F, Cl, Br, alkyl, substituted alkyl, heterocyclyoalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, aralkyl, substituted aralkyl, heterocycloaralkyl, substituted heterocycloaralkyl; or R'2 and R'4 together form a bridge; each of R5 and R6 is independently alkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, hetaryl, substituted hetaryl, hetarylalkyl, substituted hetarylalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkanoyl, substituted alkanoyl, trialkylsilyl or substituted trialkylsilyl; or when R5 and R6 are on the same nitrogen, R5 and R6 may be taken together with the nitrogen to which they are bound to form a heterocyclyl ring or a substituted heterocyclyl ring R'4 is H or together with R'2 forms a bridge; and R5 represents a protecting group; the process comprising: (a) providing the compound of formula I in a polar solution comprising a polar organic solvent; (b) adding a basic compound and a first portion of water to the polar solution; (c) contacting the polar phase with a first apolar organic phase; (d) removing the first apolar organic solvent from the polar phase; (e) adding a second portion of water to the polar phase and contacting the polar phase with a second apolar organic phase, said polar phase and said apolar organic phase remaining in contact for a period sufficient to extract the compound of formula I into the second apolar organic phase; and (f) separating the second apolar organic phase from the polar phase. 46. The process of claim 45, wherein step (e) comprises, in order, substeps: (1) adding a second portion of water to the polar phase; and (2) contacting the polar phase with a second apolar organic phase. 47. The process according to claim 46, wherein the polar phase comprises dimethylformamide. 48. The process according to claim 46, wherein the second apolar organic phase comprises toluene. 49. The process of claim 45, wherein step (e) comprises, in order, substeps: (1) contacting the polar phase with a second apolar organic phase; and (2) adding a second portion of water to the polar phase. 50. The process of claim 49, wherein the second apolar organic phase comprises isopropyl ether or t-butyl methyl ether. 51. The process of claim 49, wherein the polar phase comprises acetonitrile. 52. The process according to claim 45, wherein G4 is DMT. 53. The process according to claim 45, wherein R'2 is H, methoxy or methoxyethoxy. 54. The process according to claim 45, wherein R'2 is methoxyethoxy. 55. The process according to claim 45, wherein Bx is an optionally protected nucleobase. 56. The process according to claim 45, wherein Bx is optionally protected adenosinyl, cytidinyl, guanosinyl, 5-methyluridinyl, uridinyl, 5-methylcytidinyl. 57. The process according to claim 56, wherein Bx is N6-benzoyladenosinyl, N4-benzoyl-5-methyl-cytidinyl, N4-isobutyrylguanosinyl or 5-methyluridinyl. 58. The process according to claim 45, wherein G4 is DMT; R'2 is H, methoxyethoxy or methoxy; and Bx is N 6-benzoyladenosinyl, N4-benzoyl-5-methyl-cytidinyl, N 4-isobutyrylguanosinyl or 5-methyluridinyl. 59. The process according to claim 45, wherein the first apolar organic solvent comprises alkanes or aryl hydrocarbons. 60. The process according to claim 59, wherein the first apolar organic solvent comprises hexanes, heptane, cyclohexane or methycyclohexane. 61. The process according to claim 59, wherein the first apolar organic solvent comprises hexanes. 62. The process according to claim 45, wherein the polar solvent comprises acetonitrile, N,N-dimethylformamide or dichloromethane. 63. The process according to claim 62, wherein the polar solvent comprises N,N-dimethylformamide. 64. The process according to claim 45, wherein the basic compound of step (b) is an amine. 65. The process according to claim 64, wherein the basic compound of step (b) is a tertiary amine. 66. The process according to claim 65, wherein the basic compound of step (b) is triethyl amine. 67. The process according to claim 45, wherein the second apolar organic solvent comprises a mixture of saturated alkanes and aryl hydrocarbons. 68. The process according to claim 67, wherein the second apolar organic solvent comprises a mixture of hexanes and toluene. 69. A process of purifying a phosphoramidite by reverse precipitation at room temperature, said process comprising: (a) combining an intermediate purity phosphoramidite with a volume of an alkylated benzene solvent to form an organic solution; (b) gradually adding to the organic solution an apolar organic solvent until the phosphoramidite forms a gum phase that is discrete from the organic solution; and (c) separating the organic solution from the gum phase, said gum phase containing a purified phosphoramidite. 70. A process of claim 69, optionally comprising repeating steps (a)-(c) from about 1 to about 3 times. 71. The process of claim 70, wherein the slightly polar organic solvent comprises toluene. 72. The process of claim 71, wherein the apolar organic solvent is selected from hexane and heptane. 73. The process of claim 72, wherein the apolar organic solvent is separated from the gum phase by decanting.