Cyclopentanone → 4-(1-Hydroxycyclopentyl)-3-methylbenzoic acid

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

4-Bromo-3-methyl-benzoic acid (4.00 g, 18.6 mmol) was dissolved in tetrahydrofuran (80 mL) and the solution was cooled to −78° C. n-Butyllithium (16.4 mL of 2.5 M in hexanes, 40.9 mmol) was added dropwise over 20 min while maintaining the internal temperature below −65° C. resulting in a thin, light yellow slurry. The reaction mixture was allowed to stir for 30 min at −78° C. Cyclopentanone (1.57 g, 1.65 mL, 18.6 mmol) was then added in a dropwise manner. The mixture was stirred at −78° C. for 30 min, warmed to room temperature and stirred for 2 h. The reaction mixture was then diluted with 1 M NaOH (100 mL) and washed with diethyl ether. The organic layer was discarded and the aqueous layer was acidified with 4 M HCl to <pH 3. The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was filtered through silica gel eluting with 0-10% methanol/dichloromethane, and all product containing fraction concentrated in vacuo. The resulting solid was slurried in dichloromethane and filtered to provide 4-(1-hydroxycyclopentyl)-3-methylbenzoic acid (1.10 g, 26%) as a white solid. ESI-MS m/z calc. 220.10994. Found 221.5 (M+1)+; Retention time: 1.16 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 7.70 (d, J=1.4 Hz, 1H), 7.67 (dd, J=8.1, 1.7 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 4.77 (s, 1H), 2.54 (s, 3H), 2.07-1.98 (m, 2H), 1.98-1.89 (m, 2H), 1.87-1.77 (m, 2H), 1.72-1.59 (m, 2H).

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