Process for preparing phosphorodiamidites
View Patent ↗A method of phosphorodiamidite production comprising the steps of reacting a phosphorus trihalide with a dialkyl amine in a polar solvent to form an intermediate compound. This intermediate compound is then subsequently reacted with an hydroxylalkyl compound and a dialkyl amine in the presence of a non-polar cosolvent. Following filtration to remove the solid by-product the two solvents form separate layers. This is advantageous as the upper, non-polar solvent, layer contains the high-purity phosphorodiamidite product.
1. A method of phosphorodiamidite production which method comprises the steps of reacting a phosphorus trihalide with a dialkylamine in a polar solvent to form an intermediate compound and subsequently reacting the intermediate compound with a hydroxyalkyl compound and a dialkyl amine, in the presence of a non-polar cosolvent.
2. A method as claimed in claim 1 in which the phosphorus trihalide is phosphorus trichloride.
3. A method as claimed in claim 1 in which the phosphorus trihalide is phosphorus tribromide.
4. A method as claimed in claim 1 in which the dialkyl amine is diisopropylamine.
5. A method as claimed in claim 1 in which the dialkyl amine is selected from the group consisting of dimethylamine, diethylamine, di-n-propylamine, di-n-butylamine, di-isobutylamine or ditert-butylamine.
6. A method as claimed in claim 1 in which the polar solvent is a nitrile compound.
7. A method as claimed in claim 6 in which the nitrile compound is acetonitrile.
8. A method as claimed in claim 6 in which the polar solvent is propionitrile or benzonitrile.
9. A method as claimed in claim 1 in which the hydroxyalkyl compound is hydroxypropionitrile.
10. A method as claimed in claim 1 in which the hydroxyalkyl compound is methanol or tert-butyl alcohol.
11. A method as claimed in claim 1 in which the alkane cosolvent is a C 5 to C 9 aliphatic hydrocarbon.
12. A method as claimed in claim 1 in which the alkane co-solvent is an alicyclic hydrocarbon.
13. A method as claimed in claim 1 in which the ratio of polar solvent to non-polar solvent is 1:1.