Triethylamine → (1-{4-[4-(2-Benzyloxycarbamoyl-ethyl)-phenoxy]-benzyl}-2-morpholin-4-yl-2-oxoethyl)-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

The acid 14 (2.0 g, 4.0 mmol) was dissolved in dry DMF (35 mL) and cooled to 0-5° C. 1-Hydroxybenzotriazole (0.6 g, 4.4 mmol), EDCI (0.77 g, 4.0 mmol), and triethylamine (1.68 mL, 12.0 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (0.7 g, 4.4 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in EtOAc (100 mL). The organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL). The resulting EtOAc layer was dried and concentrated to yield the crude product. Flash chromatography on silica gel (hexanes:ethyl acetate—1:1 containing 1% acetic acid) yielded the desired benzyl hydroxamate 15 (1.6 g, 66%). 1H NMR (400 MHz, DMSO-d6): 10.93 (s, 1H), 7.28-7.35 (m, 5H), 7.19 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.68 (s, 2H), 4.52 (m, 1H), 3.21-3.49 (m, 8H), 2.72-2.80 (m, 4H), 2.21 (t, J=7.6 Hz, 2H), 1.29 (s, 9H).

Provenance & Evidence