Ethyl bromoacetate → 2-(4-(5-(2-Cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)acetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (203 mg, 0.535 mmol) in DMF (5 mL), NaH (43 mg, 1.07 mmol, 60% in mineral oil) is added at 0° C. The mixture is stirred at 0° C. and ethyl bromoacetate (98 mg, 0.588 mmol) is added. Stirring is continued at 0° C. for 30 min, then at rt for 72 h. The reaction is quenched by adding water (2 mL) and the mixture is concentrated. The residue is dissolved in THF (10 mL), methanol (10 mL) and 2 N aq. LiOH (10 mL). The mixture is stirred at 60° C. for 2 h before it is cooled to rt, acidified by adding 2 N aq. HCl and extracted three times with EA (3×20 mL). The combined org. extracts are concentrated and the crude product is purified by prep. HPLC to give the title compound (146 mg) as a white solid; LC-MS: tR=1.14 min, [M+H]+=438.07; 1H NMR (CDCl3): δ 7.90 (s, 1H), 7.88 (s, 1H), 7.79 (s br, 1H), 7.50 (s, 1H), 7.29 (s, 1H), 4.57 (s, 2H), 4.01 (s, 3H), 3.20-3.29 (m, 1H), 2.79 (q, J=7.5 Hz, 2H), 2.42 (s, 3H), 2.04-2.16 (m, 2H), 1.82-1.95 (m, 4H), 1.68-1.80 (m, 2H), 1.34 (t, J=7.5 Hz, 3H).

Provenance & Evidence