Sodium Iodide → 5-acetyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

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Reaction Steps

Bismuth (III) chloride (0.1 mmol) and sodium iodide (0.3 mmol) are transferred to a dried flask under nitrogen and 5 mL of a mixture of CH2Cl2/ether (9/1) is added by a syringe. This is followed by the addition of acetyl chloride (2.2 mmol) and the suspension is stirred for 5 min at RT. 4-trimethylsilanyloxy-7,8-dihydro-6H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2 mmol) in 5 mL of the same solvent mixture is added. After 2 hours at RT, the mixture is quenched with 20 mL saturated NaHCO3 solution and extracted several times with CH2Cl2. The organic layers are combined, dried over Na2SO4 and evaporated in vacuo yielding 5-acetyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester as an oil (86%). LRMS 363.4 found (M+1) 364.2 Step 3: In a sealed tube are 5-acetyl-4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (1.1 mmol) and formamidine acetate (5.5 mmol) and 10 mL EtOH. The mixture is heated at 120° C. for 48 hours. The solvent is evaporated in vacuo and the residue is taken up in CH2Cl2 and washed two times with NaHCO3 (aq). The organic layer is dried over Na2SO4 and evaporated in vacuo and the residue chromatographed using 10% MeOH in CH2Cl2 as mobile phase to yield 7-Methyl-3,4,5,6-tetrahydro-3,8,10-triaza-benzo[e]azulene-1-carboxylic acid ethyl ester (36%). LRMS 271.1 found (M+1) 272

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