[CH3:1][O:2][C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13]([OH:15])=O)([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)=[O:4].C(Cl)(=O)C(Cl)=O.[CH3:22][N:23](C=O)C.CN>C(Cl)Cl>[CH3:22][NH:23][C:13]([C:8]12[CH2:11][CH2:12][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH2:10][CH2:9]1)[CH2:6][CH2:7]2)=[O:15]4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid 1-A (Chapman, N. B. et al. J. Org. Chem., 1970, 35, 917) (4.0 g, 18.9 mmol) was dissolved in 12 mL of anhydrous methylene chloride under a nitrogen atmosphere, treated with oxalyl chloride (2M in methylene chloride, 28 mL, 56 mmol) and subsequently with 0.5 ml of DMF. The reaction was stirred at room temperature under a nitrogen atmosphere for 90 min, then evaporated and placed under vacuum for 20 min. The reaction was concentrated and stripped from toluene 3 times. The acid chloride was dissolved in anhydrous methylene chloride (75 mL), cooled in an ice-bath, and then treated dropwise with a solution of methylamine (2M in THF, 57 mL, 113 mmol). Upon addition of the amine, the cooling bath was removed and the reaction stirred at ambient temperature for 30 min. The mixture was diluted with 1000 mL of methylene chloride and washed with 1N aqueous HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated. Product was purified by flash silica gel chromatography, eluting with a 0-5% MeOH/CH2Cl2 gradient to yield 1-B as a white solid. MS (ESI+)=226.2 (M+1).
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