Ethanolamine → 7-beta-D-galactopyranosyloxycoumarin-4-acetic acid-(2-hydroxyethyl)amide

Participants

Reaction Steps

10 mg (0.026 mmoles) 7-β-D-galactopyranosyloxycoumarin-4-acetic acid 4 (prepared as described in Scheme 1) was dissolved in 2 ml of DMF (dimethyl formamide) and stirred under nitrogen (N2). Pyridine (0.075 ml, 0.92 mmoles) was added to the above solution followed by pentafluorophenyl trifluoromethyl acetate (0.1 ml, 0.58 mmoles) and stirred for 3 hrs. The formation of the intermediate was confirmed by thin layer chromatography (TLC) (i-PrOH/EtOH/NH4OH/water in ratio 60/35/5/20). The TLC plate was visualized by spraying a mixture of (anisaldehyde/H2SO4 /EtOH/CH3COOH in the ratio of 1/1/18/2 drops) and heating on a hot plate. The Rf of intermediate was 0.53 and the Rf of the starting carboxylic acid was 0.4. Ethanolamine (0.1 ml) was then added to the intermediate and stirred for 12 hrs. The formation of the amide was confirmed by TLC. The Rf of the amide was 0.33. The reaction solvent was evaporated to dryness and the slightly yellowish residue was dissolved in 1.5 ml of 50/50 water/CH3CN purified on a C-8 preparatory HPLC (high performance liquid chromatography) column using a gradient of 5/95 CH3CN/water (0.1% TFA) to 30/70 CH3CN/water (0.1% TFA) in 25.5 min. The peak eluting at 14 min. was collected and the solvent lyophilized to give 6 mg of a white fluffy powder giving a yield of 54%. 1HNMR (DMSO-d6);δ 3.12 (q, 2H, CH2 --CH2 --OH), 3.39 (q, 2H, HN--CH2 --CH2), 3.42-3.66 (m, 6H, H-2,3,4,5,6,6), 3.62 (s, 2H, coumarin--CH2 --), 4.71 (t, 1H, --CH2 --CH2 --OH), 4.99 (d, 1H, anomeric proton, J1,2 of 7.8 Hz confirms β-configuration), 4.54, 4.67, 4.91, 5.24 (d,t,d,d, 1H,1H,1H, 1H, 2--OH, 3--OH, 4--OH, 6--OH), 7.01 (dd, 1H, coumarin H-6), 7.04 (d, 1H, coumarin H-8), 7.6 (d, 1H, coumarin H-5), 8.26 (t, 1H, amide proton). Mass Spectroscopy (MS) (ESI): for Mol. Formula C19H23NO10Calcd. 425, H found (M+Na)+ 448.

Provenance & Evidence