Process of making phosphordiamidite compounds

1. A method of producing cyanoalkyl tetraalkylphosphordiamidite comprising:

a) reacting phosphorus trihalide with cyano-containing reagent selected from the group consisting of cyanoalkanol and cyanoalkoxytrialkylsilane to form cyanoalkylphosphordihalidite;

b) reacting the cyanoalkylphosphordihalidite with a dialkylamine to form cyanoalkyl tetraalkylphosphordiamidite and an amine hydrohalide byproduct at least a portion of which is in the form of a precipitate;

c) removing the amine hydrohalide precipitate by filtration to form a filtrate which may contain dissolved amine hydrohalide; and

d) treating the filtrate with a substance capable of removing any dissolved amine hydrohalide from the filtrate selected from the group consisting of adsorbents and polymer-supported neutralizing agents.

2. The method of claim 1 wherein the adsorbents are selected from the group consisting of alumina, silica gel, Florisil, Decalite and combinations thereof.

3. The method of claim 1 wherein the polymer-supported neutralizing agents are selected from the group consisting of triethylammonium methylpolystyrene carbonate and N, N-(diisopropyl) aminomethylpolystyrene.

4. The method of claim 1 further comprising removing the adsorbent containing the amine hydrohalide.

5. The method of claim 1 wherein the phosphorus trihalide is phosphorus trichloride.

6. The method of claim 1 wherein the alkanol group of the cyanoalkanol has from 1 to 6 carbon atoms.

7. The method of claim 6 wherein the alkanol group is ethanol.

8. The method of claim 1 wherein the alkoxy and alkyl groups of the cyanoalkoxytrialkylsilane have from 1 to 6 carbon atoms.

9. The method of claim 8 wherein the alkoxy group is ethoxy and the alkyl group is methyl.

10. The method of claim 1 wherein the alkyl group of the dialkylamine has from 1 to 6 carbon atoms.

11. The method of claim 1 further comprising neutralizing the hydrohalide by the addition of an excess of a neutralizing amine to precipitate at least a portion of the amine hydrohalide.

12. The method of claim 11 wherein the neutralizing amine is selected from the group consisting of dialkylamines and tertiary amines.

13. The method of claim 1 wherein the adsorbent is employed in the presence of a solvent.

14. The method of claim 13 wherein the solvent is selected from the group consisting of tetrahydrofuran, diethyl ether, toluene, hexane and mixtures thereof.

15. The method of claim 1 wherein the substance capable of removing dissolved amine hydrohalide is a polymer-supported neutralizing agent.

16. The method of claim 15 wherein the polymer-supported neutralizing agent is selected from the group consisting of triethylammonium methylpolystyrene carbonate and N, N-(diisopropyl)aminomethylpolystyrene.