4-(3-Adamantan-1-yl-ureido)butyric acid → 10-[4-(3-Adamantan-1-yl-ureido)-butyryloxy]-decanoic acid ethyl ester

Participants

Reaction Steps

A mixture of 10-hydroxydecanoic acid (0.25 g, 1.33 mmol; 11-hydroxyundecanoic acid for compound 881 and 12-hydroxydodecanoic acid for compound 882), ethyl bromide (0.16 g, 1.46 mmol), and lithium carbonate (0.11 g, 1.46 mmol) in DMF (25 mL) was stirred at 70 C for 6 h. Then the product was extracted with ether (30 mL), and the ether solution was washed with 1 N NaOH aqueous solution (20 mL) and water (30 mL), dried over Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane and ethyl acetate (3:1) to give 10-hydroxydecanoic acid ethyl ester (80 mg, 28%). This alcohol was coupled with 4-(3-adamantan-1-yl-ureido)butyric acid 822 by using EDCI/DMAP coupling reagent to give 880 (0.11 g, 60%) as a solid: 1H NMR (CDCl3) 1.24-1.32 (13H, m), 1.62-1.68 (10H, m), 1.80 (2H, quint, J=6.9 Hz), 1.94-1.97 (6H, m), 2.05-2.07 (3H, m), 2.28 (2H, t, J=6.9 Hz), 2.36 (2H, t, J=6.9 Hz), 3.16 (2H, q, J=6.9 Hz), 4.05-4.14 (5H, m), 4.25 (1H, s); LC-MS (ESI) m/z calcd for C27H46N2O5 [M+H]+ 479.34. found [M+H]+ 479.29; mp 60-61 C. Anal. Calcd for C27H46N2O5: C, 67.75; H, 9.69; N, 5.85. Found: C, 68.33; H, 9.92; N, 5.97.

Provenance & Evidence