Potassium Phosphate, Tribasic → (2R/S)-2-[4-(2-Hydroxy-2-methylpropyl)-phenyl]-propionic acid methyl ester

Beteiligte Stoffe

Reaktionsschritte

Experimental description: 150 mg ibuprofen methyl ester were dissolved in 1.4 mL ethanol and added to 150 mL potassium phosphate buffer pH 8.0. Var3-4 was added to the mixture at a final concentration of 3 μM. The mixture was split in 4 mL-aliquots into 15 mL scintillation vials equipped with a stir bar. 500 μL 10 mM NADPH in KPi buffer were added to each vial and stirred for 2 minutes. 500 μL cofactor regeneration solution containing 500 mM glucose-6-phosphate and 10 units/mL glucose-6-phosphate dehydrogenase were then added to each vial. The resulting mixtures were stirred at room temperature. After 48 hours, the reaction mixtures were joined together and extracted with chloroform (3×50 mL). The organic phase was then dried over magnesium sulfate (MgSO4) and evaporated in vacuo. Purification of the resulting oil by silica gel chromatography (5-40% ethyl acetate/hexane) afforded the activated product (methyl 2-(4′-(2″-hydroxy-2″-methylpropyl)phenyl)propanoate, 81 mg). 15 mg (0.06 mmol) of activated product were dissolved in 2 mL dry dichloromethane (CH2Cl2) and a catalytic amount (4 drops) of ethanol was added to the solution. The solution was cooled to −78° C. (dry ice) and added with 11 μL DAST (0.72 mmol). The reaction was stirred in dry ice for 16 hours. The reaction mixture was then added with 5 mL saturated sodium bicarbonate (NaHCO3) and extracted with dichloromethane (3×15 mL). The organic phase was then dried over magnesium sulfate (MgSO4) and evaporated in vacuo. Purification of the resulting oil by silica gel chromatography (0-30% ethyl acetate/hexane) afforded the fluorinated product, methyl 2-(4′-(1″-fluoro-2″-methylpropyl)phenyl)propanoate (7 mg, 45% yield, colorless oil). 1H-NMR (300 MHz, CDCl3): δ 1.28 (s, 3H, CH3), δ 1.35 (s, 3H, CH3), δ 1.48 (d, J=6.9 Hz, 3H, CH3), δ 2.87 (d, J: 20.4 Hz, 2H), δ 3.65 (s, 3H, OCH3), δ 3.70 (q, J=7.15 Hz, 1H), δ 7.17 (m, 4H); 13C-NMR (75 MHz, CDCl3): δ 18.80, 26.83 (d, J: 24.2 Hz), 45.24, 47.37 (d, J: 22.8 Hz), 52.25, 129.12 (d, J: 258.8 Hz), ca. 130, ca. 132, ca. 139, ca. 173; 19F-NMR (282 MHz, CDCl3): δ −137.7 (m). HRMS (EI+): exact mass calculated for C14H19FO2 requires m/z 238.1369, found 238.1370.

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