Tetrahydrofuran → 2-(2-(3-(4-((S)-2,3-dihydroxypropoxy)-3,5-dimethylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)-2-(4-fluorophenyl)cyclohexanone

Beteiligte Stoffe

Reaktionsschritte

A solution of 3-(1-(4-fluorophenyl)cyclohexyl)propanoic acid (20 mg, 0.08 mmol, Preparation 1C) and (R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-N-hydroxy-3,5-dimethylbenzimidamide (23.5 mg, 0.08 mmol) in dichloromethane (1.5 mL) was treated with N,N′-diisopropylcarbodiimide (15 μL, 0.096 mmol). The reaction mixture was stirred at room temperature for 2 h and then treated with a solution of 1N tetra-n-butylammonium fluoride in THF (40 μL, 0.04 mmol). After 3.5 h, the reaction mixture was concentrated and the residue was cooled to 0° C. and treated with TFA (1 mL). After 1 min, the ice bath was removed and stirring was continued for additional 1 h. The reaction mixture was concentrated and the residue was purified by reversed-phase autoprep HPLC (Phenomenex S10 30×100 mm, 40 min gradient time, Detection Wave length 220 nm, Starting solvent: 10% aq. MeOH—0.1% TFA; Final solvent: 90% aq. MeOH—0.1% TFA) to obtain 2-(2-(3-(4-((S)-2,3-dihydroxypropoxy)-3,5-dimethylphenyl)-1,2,4-oxadiazol-5-yl)ethyl)-2-(4-fluorophenyl)cyclohexanone (37.4 mg, 28% yield) as a colorless viscous oil. LC/MS: m/e 469.20 (M+H)+. 1H NMR (400 MHz, CD3OD): δ ppm 7.64 (s, 2H), 7.33-7.51 (m, 2H), 6.92-7.15 (m, 2H), 3.96-4.04 (m, 1H), 3.87-3.94 (m, 1H), 3.79-3.86 (m, 1H), 3.64-3.77 (m, 2H), 2.47-2.68 (m, 2H), 2.34 (s, 6H), 2.03-2.18 (m, 4H), 1.55-1.81 (m, 4H), 1.31-1.56 (m, 4H).

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