Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=2)[C:7]([CH:10]=O)=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4].[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[CH2:27][CH:28](C([O-])=O)[C:29]([O:31]CC)=[O:30].N1CCCCC1.[OH-].[Na+]>O.C1(C)C=CC=CC=1>[CH2:1]([C:5]1[N:6]([CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=2)[C:7](/[CH:10]=[C:28](\[CH2:27][C:23]2[S:22][CH:26]=[CH:25][CH:24]=2)/[C:29]([OH:31])=[O:30])=[CH:8][N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(=O)C(Cc1cccs1)C(=O)[O-]
Reactant: CCCCc1ncc(C=O)n1Cc1ccc(C(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCNCC1
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCc1ncc(/C=C(\Cc2cccs2)C(=O)O)n1Cc1ccc(C(=O)O)cc1
Temperature: 57.5 °C
Reaction time: 2 h

Procedure:
A glass-lined steel reaction vessel is charged with 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid, (2-thienylmethyl)propanedioic acid, mono-ethyl ester (about 1.9 molar equivalents relative to assayed 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid), and toluene (about 6.3 g per gram of assayed 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) and heated to 55-60° C. Piperdine (approximately 66 mol % relative to 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) is added. The reaction is then heated to reflux with azeotropic removal of water under reduced pressure so that an internal temperature of about 70-75° C. is maintained. The reaction is monitored by IPC 1 for the disappearance of starting 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid. If >10% of the starting 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid remains after 12-30 hours, additional charges of (2-thienylmethyl)propanedioic acid, mono-ethyl ester (0.10 equivalents per charge relative to 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) may be added and the reaction continued. When IPC 1 analysis indicates that the reaction of starting 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid is essentially complete (<10% remaining), the solution is cooled to about 60-65° C. The cooled solution is treated with demineralized water (6.8 g per gram of assayed 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) and an aqueous, 6.7 N, solution of sodium hydroxide (about 2.0 ml of solution per gram of assayed 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) and the mixture is heated at reflux for about 1.0-3.5 hours. The reaction is assayed, by IPC 2, to confirm the complete conversion (<2.0%) to product. The solution is then cooled to about 50° C. and the layers are separated. Ethyl alcohol (about 5.0 g per gram of assayed 4-[(2-n-butyl-5-formyl-1H-imidazol-1-yl)methyl]benzoic acid) is added to the aqueous phase and the pH is adjusted to about 5.0-5.4 with aqueous, 6 N, hydrochloric acid solution. The resulting suspension is stirred at about 10-15° C. for about 2 hours to complete precipitation. The product is isolated by centrifugation, washed twice with water and the wet cake is used directly in the next step. The corrected isolated yield of product at this stage is typically about 70-85%. Assay of a dried sample of product on a w/w basis by HPLC versus a standard sample typically indicates a relative purity of about 97-99%.