Benzyl chloroformate → 2-[3-[2-[benzyloxycarbonyl-[4-(pyridin-3-yl)butyl]amino]ethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid ethyl ester

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Reaction Steps

A solution of 3.00 g (theoretical maximum of 5.86 mmol) of crude 2-[2-(3,5-dimethylphenyl)-3-[2-[4-(pyridin-3-yl)butylamino]ethyl]-1H-indol-5-yl]-2-methylpropionic acid ethyl ester in 30 ml of dry CH2Cl2 was stirred under N2 with cooling in a dry-ice-acetone bath. To this solution was added by syringe 1.106 ml (820 mg, 6.36 mmol) of N,N-diisopropylethylamine. Then 956μ (1.14 g, 6.36 mmol) of benzyl chloroformate was added dropwise by syringe over 5-10 minutes. After 20 minutes, the solution was removed from the cooling bath and allowed to warm to room temperature. After 2 hours, the solution was diluted with 50 ml of CH2Cl2, transferred to a separatory funnel, and shaken with 80 ml of H2O. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. Flash chromatography of the residual gum on silica gel (gradient elution with 0.2-2% MeOH in CH2Cl2) gave 2.81 g (55% overall for Steps 1 and 2) of pale, golden-yellow gum; virtually homogeneous by TLC in 95:5 CH2Cl2 -MeOH. 500 MHz 1H NMR (CDCl3) was complex, owing to rotamers, but appeared to be consistent with the assigned structure. Mass spectrum (ESI): m/e 646 (M+H)+.

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