C(NC(C)C)(C)C.CC(C)([O-])C.[K+].C([Li])CCC.[CH3:19][C:20]1[C:21]([C:26]([OH:28])=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=1.[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33]Cl.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C(N(CC)CC)C>[ClH:29].[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=1)[CH2:33][CH2:19][C:20]1[C:21]([C:26]([OH:28])=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=1A mixture of THF (1050 mL) and diisopropylamine (320 mL, 2.29 mol) was cooled to 0° C., and potassium tert-butoxide (129 g, 1.095 mol; 95% pure) was added. The solution was cooled to −50° C. and n-butyllithium solution (2.5M in hexane, 925 mL, 2.312 mol) was added, keeping the temperature below −40° C. The solution was then stirred at −50° to −40° C. prior to the addition of a solution of 3-methylpicolinic acid of Formula I (150 g, 1.095 mol) in THF (300 mL) and triethylamine (55.3 g, 0.547 mol) at −45° to −35° C. Use of the triethylamine reduces the amount of THF needed to dissolve the compound of Formula I. The purple solution was stirred at −45° to −35° C., and 3-chlorobenzyl chloride of Formula IV (176.3 g, 1.095 mol) was added. The suspension was allowed to warm to ambient temperature overnight. The suspension was poured into a solution of potassium carbonate (150 g, 1.09 mol) in water (1150 mL), washed with an additional 200 mL of water and stirred. The suspension was filtered and the solid washed with 200 mL water. The bottom phase containing the product as the potassium salt was separated and the organic phase, washed with 100 mL water. The aqueous-solution was heated under vacuum to 60° C. to remove dissolved organic volatiles and cooled to 40° C. Concentrated hydrochloric acid (585 mL of 37%) was slowly added. The resulting suspension was cooled to 0° to 10° C., filtered and washed with 10% aqueous HCl (200 mL) to remove salts. The suspension was washed with acetone and dried to give 286.5 g (88%) of 3-(3-chlorophenethyl)-picolinic acid hydrochloride 3-CPPA.HCl (Formula IIa).
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