Propylphosphonic anhydride → 3-(3-Bromophenethoxy)-N-cyclohexyl-N-(2,2-dimethoxyethyl)propanamide

Participants

Reaction Steps

To a stirred solution of 3-(3-bromophenethoxy)propanoic acid (3.3 g, prepared as in Preparation 3, Step ii), Procedure B) in acetonitrile (60 mL) was added TEA (20.21 mL) and N-(2,2-dimethoxyethyl)cyclohexanamine (2.26 g). T3P (1.56M in THF, 15.39 mL) was then added portionwise. The reaction was stirred overnight, and then worked up by the addition of saturated sodium hydrogen carbonate, which was extracted twice with ethyl acetate. The pooled organics were washed once with water, once with brine, dried over sodium sulphate, filtered and the solvent removed to afford a brown oil, which was purified on silica (5% Ethyl acetate/isohexane to 20% Ethyl acetate/isohexane). The solvent was evaporated to afford an orange oil (4.5 g). MS [M+H-MeOH]+=410/412 (MultiMode+) 1H NMR (400 MHz, CD3OD) δ 7.40-7.35 (m, 1H), 7.33-7.29 (m, 1H), 7.20-7.12 (m, 2H), 4.54 (t, J=5.0 Hz, 0.5H), 4.39 (t, J=5.4 Hz, 0.5H), 4.08-3.98 (m, 1H), 3.73-3.59 (m, 4H), 3.39-3.36 (m, 2H), 3.37 (s, 3H), 3.34 (s, 3H), 2.83-2.78 (m, 2H), 2.67-2.61 (m, 2H), 1.82-1.74 (m, 2H), 1.70-1.55 (m, 3H), 1.55-1.42 (m, 2H), 1.38-1.26 (m, 2H), 1.19-1.04 (m, 1H), a ˜1:1 mixture of rotamers is observed.

Provenance & Evidence