Reaction SMILES: C(O)(=O)C(O)=O.[CH3:7][N:8]([CH3:29])[CH2:9][CH2:10][CH:11]([C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24]CC)=[O:23])=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1>C(O)C>[CH3:29][N:8]([CH3:7])[CH2:9][CH2:10][CH:11]([C:18]1[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:27][CH:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1
Reactant: CCOC(=O)c1ccc(C(CCN(C)C)c2ccccn2)cc1
Agent: O=C(O)C(=O)O
Solvent: CCO
Product: CN(C)CCC(c1ccc(C(=O)O)cc1)c1ccccn1
Yield: 99.5 %

Procedure:
(+/−)-Brompheniramine 17 (obtained by neutralization of the maleate salt; 38 g, 120 mmol) was dissolved in dry THF under nitrogen and the solution was cooled in a dry ice/acetone bath. n-butyllithium (1.6 M, hexanes, 90 mL, 144 mmol) was added dropwise to the reaction mixture to give a red solution. After 2 h of stirring, carbon dioxide was bubbled into the solution as the bath slowly warmed to room temperature. The resulting mixture was stirred overnight and the reaction was quenched with water (500 mL). The aqueous layer was extracted with ethyl acetate (2×500 mL). The organic layer was discarded and the aqueous layer was concentrated to a yellow paste. The paste was digested in sodium hydroxide (1 N, 150 mL) and chloroform (200 mL) and the layers were separated. The aqueous layer was extracted with chloroform (200 mL) and ethyl acetate (2×150 mL). The chloroform layers were concentrated to yield unreacted 17 (17 g, 44%). The ethyl acetate layers were concentrated to 1.4 g of a complex mixture which was discarded. The aqueous layer was concentrated to a thick oil, filtered to remove insoluble solid, and dissolved in ethanol (100 mL) and water (40 mL). The pH was adjusted to 2 by the careful addition of concentrated HCl (about 17 mL). The resulting solution was concentrated, dissolved in 1:1 methanol:ethanol, filtered to remove insoluble NaCl and concentrated to a brown oil (13 g). The oil was purified by column chromatography (8.5/1/0.5 CH2Cl2/MeOH/triethylamine) to yield 18a as a white solid (3 g, 8%). The structure was confirmed by 1H NMR, LC/MS, and elemental analysis. Ethyl 4-[3-dimethylamino-1-(2-pyridyl)propyl]benzoate (18c). Acid 18a (927 mg, 3.26 mmol) was stirred in oxalyl chloride (5 mL) at room temperature for 2 minutes and dry toluene (4 mL) was added to facilitate stirring. After 1 h, the mixture was concentrated. Ethanol (10 mL) and triethylamine (1.35 mL) were added and the dark yellow mixture was stirred overnight. The mixture was then concentrated and partitioned between ethyl acetate (25 mL) and water (25 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (10 mL). The combined organic layers were washed with water (20 mL) and the combined aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried with Na2SO4, filtered, and concentrated to yield 18c as an oil. Purification by flash chromatography (4/1 CH2Cl2/MeOH) yielded 18c (136 mg) as a yellow oil. The structure was confirmed by 1H NMR and LC/MS. (Esters 18d, 18e, and 18f were similarly prepared.) Ethyl 4-(3-dimethylamino-1-(2-pyridyl)propyl)benzoate, oxalic acid salt (18c-Ox). A solution of oxalic acid (52 mg, 0.58 mmol) in ethanol (0.5 mL) was added in one aliquot to a stirred solution of 18c (185 mg, 0.59 mmol) in ethanol (0.5 mL). The mixture became solid after 30 seconds of stirring. The solid mass was broken up, ethanol (0.75 mL) was added, and the solid was collected by suction filtration after 1.5 h of stirring and subsequently washed with ethanol. After drying, the oxalate salt 18c-Ox was obtained as white powder (167 mg, 72%). 1H NMR, LC/MS, and elemental analyses were consistent with the structure of the product. (The oxalate salt of 18e was prepared similarly.)