反应详情

To a solution of 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-ol (0.280 g, 1.10 mmol) and isopropyl 4-imidazolecarboxylate (0.121 g, 0.77 mmol), which can be prepared as described in Example 1, in THF (6 mL) at 0° C. is added triphenylphosphine (0.291 g, 1.10 mmol) and methyl azodicarboxylate (40% in toluene, 0.41 mL, 1.10 mmol). After 1 hour, the cooling bath is removed and after another hour, the mixture is diluted with ethyl acetate and washed with half-saturated brine, dried over magnesium sulfate, filtered, t and concentrated. The resulting residue is purified by semi-preparative reverse phase HPLC (5 to 100% acetonitrile/water w/0.1% TFA) to furnish affords a pale yellow oil. After free-basing, 3-(7-bromo-5-fluoro-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester is obtained; MS: (ESI) m/z 381.1, 383.0 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.37 (d, J=6.3 Hz, 3 H), 1.39 (d, J=6.3 Hz, 3 H), 1.71-1.81 (m, 1 H), 1.83-1.92 (m, 1 H), 2.07-2.24 (m, 2 H), 2.72 (dt, J=17.7, 6.8 Hz, 1 H), 2.87 (dd, J=17.7, 5.8 Hz, 1 H), 5.22 (sept, J=6.3 Hz, 1 H), 6.29 (t, J=5.2 Hz, 1 H), 6.94 (br. s, 1 H), 7.18 (dd, J=8.8, 1.8 Hz, 1 H), 7.22 (s, 1 H), 7.79 (s, 1 H).

1. customthe cooling bath is removed and after another hour
2. additionthe mixture is diluted with ethyl acetate
3. washwashed with half-saturated brine
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationt and concentrated
7. customThe resulting residue is purified by semi-preparative reverse phase HPLC (5 to 100% acetonitrile/water w/0.1% TFA)
8. customto furnish
9. customaffords a pale yellow oil