Trifluoroacetic acid → HCID 57797482, compound

Participants

Reaction Steps

To the solution of 5-(2,4-difluoro-phenoxy)-2-(2-ethoxy-vinyl)-benzoic acid methyl ester 9 (194 mg, 0.6 mmol) in dichloromethane (5 mL) was added 1 mL of TFA and five drops of water. The reaction was stirred at room temperature for ten minutes, at which time the solvent was removed. The reaction mixture was re-suspended in dichloroethane and 4-(2-amino-3-methyl-butoxy)-piperidine-1-carboxylic acid tert-butyl ester A11 (200 mg, 0.70 mmol), DIEA (154 mL, 0.87 mmol), and sodium triacetoxyborohydride (184 mg, 1.87 mmol) were added. The mixture was stirred at room temperature for fifteen minutes and then at 60° C. for additional 16 hours. The reaction was diluted with 100 mL CH2Cl2 and extracted with saturated brine (100 mL). The organic layer was concentrated and loaded onto a silica gel column and eluted with 2% methanol in dichloromethane to give 250 mg (79%) of 4-{2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butoxy}-piperidine-1-carboxylic acid tert-butyl ester 15 as light yellow solid. TLC, Rf=0.3 (2% MeOH CH2Cl2). 1H NMR (CDCl3) δ 0.92 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.5 Hz, 3H), 1.31 (m, 1H), 1.44 (s, 9H), 1.61 (m, 2H), 2.2 (m, 1H), 2.90 (m, 2H), 3.14 (m, 2H), 3.41(m, 1H), 3.51 (m, 1H), 3.73 (m, 1H), 2.63 (m, 4H), 4.02 (m, 1H), 4.56 (m, 1H), 6,84 (m, 1H), 6.93 (m, 1H), 7.06 (m, 2H), 7.14 (d, J=8.1 Hz, 1H), 7.54 (d, J=2.6 Hz, 1H), M+1 found 545.3; C30H38F2N2O5 requires 544.27.

Provenance & Evidence