Trifluoroacetic acid → Sodium Carbonate

Participants

Reaction Steps

A solution of cis-2-(tert-butoxycarbonylamino)-cyclohexane carboxylic acid (255 mg, 1.05 mmol) in pyridine (10 ml) was stirred at RT. 6-chloro-9H-β-carbolin-8-ylamine (218 mg, 1.00 mmol) was added, followed by EDCI (315 mg, 1.64 mmol) and the slightly turbid pale orange solution was stirred at RT for 16 hr. The solution was diluted with H2O (20 ml) and poured into a separatory funnel containing H2O (50 ml) and EtOAc (50 ml). The mixture was shaken and the layers were separated. The aqueous layer was extracted with EtOAc (50 ml) and the combined organic layers were washed with brine. The organic layer was dried, filtered and concentrated to yield a yellow oil which was placed under high vacuum for 4 hr. The resulting yellow-brown glass was slurried in CH2Cl2 (10 ml) at RT. Trifluoroacetic acid (5 ml) was added and the slurry instantly dissolved to form a clear orange solution. The solution was stirred at RT for 45 min, then concentrated to a brown residue. The residue was azeotroped from toluene (3×10 ml) to yield a yellow solid. A solution of dilute aqueous Na2CO3 was prepared by adding a small volume of 10% aqueous Na2CO3 to H2O (50 ml) until the aqueous solution reached a pH of 10. The yellow solid was dissolved in minimal MeOH and was added drop-wise to the aqueous solution with stirring. The precipitate which formed was filtered, washed with H2O and placed under high vacuum to yield 2-amino-cyclohexanecarboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide as pale yellow solid (147 mg). 1H-NMR (300 MHz, DMSO-d6): δ 9.00 (s, 1); 8.37-8.34 (m, 1); 8.16-8.13 (m, 2); 7.83 (m, 1); 5.66-5.00 (br s, 2); 3.42-3.40 (m, 1); 2.70-2.62 (m, 1); 2.02-1.90 (m, 1); 1.70-1.54 (m, 5); 1.42-1.29 (m, 2). NH4OAc standard conditions. DAD Rf=1.46 min. M+H=343.

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