Trifluoroacetic acid → HCID 68829327, compound

Participants

Reaction Steps

To a solution of 5-(2,4-difluoro-phenoxy)-2-(2-ethoxy-vinyl)-benzoic acid methyl ester 9 (1.2 g, 3.8 mmol) in dichloroethane (20 mL) was added 5 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 crude reaction mixture was re-suspended in dichloroethane and D-valine t-butylester HCl (2.05 g, 9.75 mmol), triethylamine (1.36 mL, 9.75 mmol), and tiacetoxyborohydride (2.76 g, 13 mmol) were added. The reaction was stirred at room temperature for fifteen minutes and then at 60° C. for an additional 16 hours. The mixture was diluted with 100 mL dichloromethane and extracted with saturated brine (100 mL). The organic layer was concentrated, loaded onto a silica gel column and eluted with dichloromethane to yield 516 mg (77%) of 2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butyric acid tert-butyl ester 10 as a light yellow solid. TLC, Rf=0.3 (2% MeOH CH2Cl2); 1H NMR (CDCl3) δ 0.93 (d, J=6.7 Hz, 3H), 1.05 (d, J=6.6 Hz, 3H), 1.45 (s, 9H), 2.24 (m, 1H), 2.93 (m, 2H), 3.52 (m, 1H), 3.75 (m, 1H), 5.00 (d, J=6.7 Hz, 1H), 6.85 (m, 1H), 6.93 (m, 1H), 7.07 (m, 2H), 7.15 (d, J=8.3 Hz, 1H), 7.58 (d, J=2.6 Hz, 1H). M+1 found 432.10; C24H27F2NO4 requires 431.19.

Provenance & Evidence