C([O:3][C:4]([C:6]1([C:15](=[O:27])[NH:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH2:19][CH2:20][NH:21][CH2:22]3)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])C.O1CCOCC1.CO.O>CO.C(Cl)Cl>[CH2:22]1[C:23]2[C:18](=[C:17]([NH:16][C:15]([C:6]3([C:4]([OH:5])=[O:3])[CH2:14][C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[CH2:7]3)=[O:27])[CH:26]=[CH:25][CH:24]=2)[CH2:19][CH2:20][NH:21]1A 250 mL round bottom flask containing 2-(1,2,3,4-tetrahydro-isoquinolin-5-ylcarbamoyl)-indan-2-carboxylic acid ethyl ester (322, 440 mg, 1.21 mmoles) is charged with 1,4-dioxane (7 mL) and MeOH (7 mL). A stirring bar is added and stirring is initiated. After dissolution, water (3.5 mL) is added followed by the LiOH monohydrate (128 mg, 3.05 mmol). After 18 h, tlc analysis (silica, 10% MeOH/DCM) indicates that the starting material is completely consumed. Amberlyst highly acidic exchange resin (1 g) is added to the reaction flask. The reaction is capped and allowed to stir at ambient temperature. After 24 h, the contents of the flask are filtered through a pad of Celite. The solvent is removed from the filtrate. The resultant residue is reconstituted with iPrOH/toluene (1:1, 25 mL). The solvent is removed in vacuo. This process is repeated twice. Pumping to constant weight provides an off-white solid (400 mg, 99%).
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