反应详情

To a solution of methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-carbonyl}cyclopentanecarboxylate (4.24 g, 11.48 mmol) in methanol (34 mL) was added conc. HCl (11.4 mL), and the resulting solution was stirred at rt for 2 h. Solvent was then removed, the residual mixture was dissolved in water, and the acidity of the mixture was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution. The mixture was then extracted with dichloromethane and washed with saturated sodium chloride solution, dried over sodium sulfate, and the solvent was removed in vacuo. The crude mixture was then triturated with ethyl acetate/hexane to afford methyl 2-[(4′-amino-3′-fluoro-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylate (3.5 g, 89%, 80% ee). LC-MS ret. time 3.00 min, m/z 370.0 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.52-1.84 (m, 4H), 1.97-2.02 (m, 1H), 2.14-2.18 (m, 1H), 3.24-3.33 (m, 1H), 3.56 (s, 3H), 4.08 (q, 1H), 5.47 (br s, 2H), 6.84 (t, 1H), 7.34 (dd, 1H), 7.48 (dd, 1H), 7.78 (d, 2H), 7.99 (d, 2H).

1. customSolvent was then removed
2. dissolutionthe residual mixture was dissolved in water
3. additionthe acidity of the mixture was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution
4. extractionThe mixture was then extracted with dichloromethane
5. washwashed with saturated sodium chloride solution
6. dry with materialdried over sodium sulfate
7. customthe solvent was removed in vacuo
8. customThe crude mixture was then triturated with ethyl acetate/hexane