Hydrochloric Acid → (+/-)-(E)-ethyl 2-(7-bromo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate

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Reaktionsschritte

A solution of (±)-ethyl 2-(7-bromo-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate TFA salt (31 mg, 0.07 mmol) in CH2Cl2 was treated with MP-carbonate resin (2.89 mmol g−1, 200 mg, 0.58 mmol). The mixture was stirred for 0.5 h and filtered. To the filtrate were added ortho-(trifluoromethyl)cinnamic acid (42 mg, 0.19 mmol), i-Pr2NEt (0.07 mL, 0.39 mmol) and solid HATU (37 mg, 0.10 mmol). The mixture was stirred at rt for 4 h. A 10-mL Chem-Elut cartridge was wetted with 5% aq HCl (6 mL) and allowed to stand for 5 min. The reaction mixture was applied and the cartridge was eluted with ether (20 mL). The eluate was passed through a second 10-mL Chem-Elut cartridge that had been prewetted with satd aq NaHCO3 (6 mL). The eluate was evaporated and the residue was purified by preparative HPLC to afford (±)-(E)-ethyl 2-(7-bromo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate (15 mg, 42%) as an oil. LC-MS Method 1 tR=2.23, min, m/z=550, 552; 1H NMR (CDCl3) 1.28 (t, 3H), 1.40-1.80 (3H), 2.43 (m, 2H), 2.76 (m, 1H), 2.91 (m, 2H), 3.18 (m, 1H), 3.34 (m, 1H), 3.62 (m, 1H), 4.14 (m, 1H), 4.19 (q, 2H), 4.80 (m, 1H), 6.83 (d, 1H), 7.11 (m, 2H), 7.35-7.75 (5H), 7.92 (m, 1H).

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