3-(2-(Trifluoromethyl)phenyl)-2-propenoic acid → (E)-1-(6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4'-piperidine]-1'-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one

Participants

Reaction Steps

To a stirred solution of 6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4′-piperidine] (570 mg, 2.45 mmol) in CH2Cl2 (20 mL) were added ortho-(trifluoromethyl)cinnamic acid (132 mg, 0.61 mmol), i-Pr2NEt (0.43 mL, 2.45 mmol), HOBt (99 mg, 0.73 mmol) and EDC.HCl (141 mg, 0.73 mmol). The mixture was stirred at rt for 3 d. The mixture was diluted with EtOAc (80 mL), washed with water (30 mL) and satd aq NaHCO3 (30 mL), and dried over Na2SO4. Removal of the solvent left an orange oil (378 mg). A portion of the oil was purified by preparative HPLC to afford (E)-1-(6-methoxy-3,4-dihydro-2H-spiro[isoquinoline-1,4′-piperidine]-1′-yl)-3-(2-(trifluoromethyl)phenyl)prop-2-en-1-one. LC-MS Method 1 tR=1.37, min, m/z=431; 1H NMR (CDCl3) 2.25 (m, 4H), 3.16 (br s, 2H), 3.39 (m, 1H), 3.45 (br s, 2H), 3.78 (s, 3H), 3.84 (m, 1H), 4.11 (m, 1H), 4.78 (m, 1H), 4.9 (1H), 6.65 (s, 1H), 6.83 (m, 2H), 7.12 (d, 1H), 7.4-7.75 (4H), 7.98 (d, 1H).

Provenance & Evidence