反应详情

A solution of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester (140.8 mg, 0.419 mmol) in tetrahydrofuran (14 mL) was treated with a warm solution of lithium hydroxide monohydrate (175.8 mg, 4.19 mmol) in water (3.5 mL). The reaction mixture was stirred at room temperature for 20 hours, diluted with water, acidified with aqueous 3.0 N HCl and extracted with ethyl acetate. The ethyl acetate layers were combined, washed with brine, dried (MgSO4), filtered and concentrated. Purification by reverse phase HPLC gave 81.7 mg (60%) of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.43 (br. s, 1 H), 7.91 (dd, J=8.7, 6.3 Hz, 1 H), 7.74 (s, 1 H), 7.62 (dd, J=12.1, 1.8 Hz, 1 H), 7.33 (td, J=8.7, 1.8 Hz, 1 H), 7.03 (d, J=7.8 Hz, 2 H), 6.92 (d, J=7.8 Hz, 2 H), 4.40 (s, 2H), 3.82 (s, 2 H), 2.32 (s, 3 H), 2.21 (s, 3 H). HRMS (ES−) cald. for C21H19FO2 [(M−H)−] 321.1296, obsd. 321.1294.

1. extractionextracted with ethyl acetate
2. washwashed with brine
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by reverse phase HPLC