Dicyclohexylcarbodiimide → 4-[5-(2-Cyclopentyl-6-methoxy-4-pyridinyl)-1,2,4-oxadiazol-3-yl]-2-ethyl-6-methylphenol

Participants

Reaction Steps

A solution of 2-cyclopentyl-6-methoxy-isonicotinic acid (21.0 g, 102 mmol), 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine (20.0 g, 103 mmol) and HOBt (1.24 g, 9 mmol) in THF (200 mL) is cooled to 5° C. before a solution of DCC (20.0 g, 97 mmol) in THF (100 mL) is added dropwise. Upon complete addition, the mixture is stirred at rt for 18 h then at 75° C. for 48 h. The solvent is evaporated and the remaining residue is dissolved in TBME (200 mL). The precipitate that forms is removed, filtered off and washed with additional TBME (200 mL). The filtrate is washed with approximately 4% aq. NaHCO3 solution (100 mL) and water (100 mL) and concentrated. The crude product is recrystallised from hot acetonitrile (200 mL) to give 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (28.6 g) as a white solid; 1H NMR (CDCl3): δ1.33 (t, J=7.5 Hz, 3H), 1.70-1.80 (m, 2H), 1.84-1.96 (m, 4H), 2.05-2.16 (m, 2H), 2.36 (s, 3H), 2.74 (q, J=7.3 Hz, 2H), 3.25 (quint, J=7.5 Hz, 1H), 4.02 (s, 3H), 5.01 (s), 7.31 (s, 1H), 7.51 (s, 1H), 7.85 (s, 2H).

Provenance & Evidence