1-Hydroxybenzotriazole → HCID 59547283, compound

Participants

Reaction Steps

To a solution of amino acid 2-((5S)-3-(aminomethyl)-1,5-bis(tert-butoxycarbonyl)pyrrolidin-3-yl)acetic acid (D6) (1.45 mmol) in CH2Cl2 (32 ml) was added 1-hydroxybenzotriazole (HOBT, 196 mg, 1.45 mmol, 1 eq), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 418 mg, 2.2 mmol, 1.5 eq), and N,N-Diisopropylethylamine (DIEA, 756 μl, 4.4 mmol, 3.0 eq). The reaction was aged at room temp. overnight. The solution was diluted with CH2Cl2 (100 ml) and washed with water (100 ml), 1N sodium hydroxide in water (100 ml) and brine (100 ml). The organics were dried over sodium sulfate, filtered, and concentrated with a second extract, to give crude product. This was purified on silica (1% to 20% MeOH/CH2Cl2 gradient) to give spirolactam (3S)-di-tert-butyl 8-oxo-2,7-diazaspiro[4.4]nonane-2,3-dicarboxylate (E6) (295 mg, 868 μmol). 1H NMR (CDCl3) δ1.35 (m, 18H), 1.91 (m, 2H), 2.3 (m, 3H), 3.2 (m, 2H), 3.3-3.5 (m, 2H), 4.10 (m, 1H), 6.21 (m, 1H); LCMS for C17H28N2O5 340.20 [M], found ES+ 341.2 [M+H]+, 285.2 [M+H, minus t-butyl]+, 285.2 [M+H, minus t-butyl, minus BOC]+ at 2.6 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes.

Provenance & Evidence