Patent ID: 8859756

Claim:
A process for preparing an enantiomerically- or a diastereomerically enriched phosphorus-containing active, salt, or pharmaceutically acceptable salt thereof, of formula I-1: which comprises the steps of: (a) reacting a protected or unprotected Active with a base to form a salt of said active and then reacting said salt with an enantiomerically- or a diastereomerically enriched compound of formula II-1 wherein the Active is a nucleoside, a nucleoside-analog, or a non-nucleoside; wherein the nucleoside is selected from wherein the nucleoside-analog is selected from wherein the non-nucleoside is selected from wherein W is an aryl or —(CH 2 ) n SC(O)C(CH 3 ) m (CH 2 OH) 3-m ; wherein n is 2 or 3 and m is 0, 1, 2, or 3; wherein LG is selected from the group consisting of halogen, tosylate, mesylate, triflate, acetate, trifluoromethylacetate, camphorsulfonate, 2-thioxobenzo[d]thiazol-3(2H)-yl, aryloxide, and aryloxide substituted with at least one electron withdrawing group; wherein R is a substituted or unsubstituted C 1-30 alkyl, a substituted or unsubstituted C 3-10 cycloalkyl, a substituted or unsubstituted C 1-30 alkylaryl, a substituted or unsubstituted C 2-10 alkenyl, a substituted or unsubstituted —OC 1-30 alkyl, a substituted or unsubstituted C 6-12 aryl; and wherein R′ is a substituted or unsubstituted C 1-30 alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted C 1-30 alkylaryl, or a substituted or unsubstituted C 6-12 aryl; and (b) optionally deprotecting the compound obtained in step (a) to obtain the enantiomerically- or diastereomerically-enriched phosphorous-containing active, salt, or pharmaceutically acceptable salt thereof of formula I-1, wherein the enantiomerically- or diastereomerically-enriched compound of formula II-1 is obtained by crystallization from a composition comprising: i. a first composition; ii. a leaving group precursor; iii. a non-nucleophilic base; and iv. a liquid composition; wherein the first composition comprises Rp-II-1 and Sp-II-1; and wherein the leaving group precursor is 2,4-dinitrophenol, 4-nitrophenol, 2-nitrophenol, 2-chloro-4-nitrophenol, 2,4-dichlorophenol, or pentafluorophenol.