T.19 Gram-scale Decarboxylative Trifluoromethylation: An oven-dried 25 mL Schlenk flask was sealed having a rubber septum and cooled under an atmosphere of dry N2. CuI (0.23 g, 1.2 mmol) was added for the vial, which was transferred into a N2-filled glovebox. Anhydrous KF (1.4 g, 24 mmol) and anhydrous KI (0.25 g, 1.five mmol) were added to the flask, which was sealed using a rubber septum and removed from the glovebox. The flask was attached to a Schlenk line, and remained open to an atmosphere of dry N2 for the remainder of your reaction (CAUTION: CO2 (g) is generated during the course from the reaction; consequently, the reaction should either be conducted within a pressure-rated vessel, or open to an inert atmosphere). MeCN (3.0 mL), MeO2CCF2Br (0.26 mL, 2.4 mmol), 1b (two.2 g, six.0 mmol), and DMF (three.0 mL) had been injected into the flask, which was placed within a pre-heated oil bath (70 ) and stirred for 24 h. Soon after cooling to space temperature, the mixture was diluted with EtOAc (75 mL). The mixture was washed with H2O (75 mL) and brine (75 mL). The organic phase was dried more than Na2SO4, filtered, as well as the solvent was removed in vacuo. The residue was purified by way of silica gel chromatography (hexanes/Et2O 39:1) to supply 2b as a colorless solid (1.four g, 87 ). The 1H and 19F NMR spectrum have been consistent with the information described above. N-(4-(2,2,2-Trifluoroethyl)phenyl)pivalamide (2c)–General Process B was followed making use of 1c (91.0 mg, 0.250 mmol). Workup and chromatographic purification (hexanes/EtOAc 1:09:1) afforded the title compound as a colorless solid (52.Price of 201929-84-2 eight mg, 81 ). mp 13233 . 1H NMR (400 MHz, CDCl3) 7.54 (d, J = 8.four Hz, two H), 7.37 (s, 1 H), 7.25 (d, J = 8.three Hz, two H), three.33 (q, J = ten.8 Hz, two H), 1.32 (s, 9 H). 13C1H NMR (101 MHz, CDCl3) 176.8, 138.1, 130.8, 125.9 (q, J = three.0 Hz), 125.eight (q, J = 276.7 Hz), 120.2, 39.76, 39.74 (q, J = 29.eight Hz), 27.7. 19F NMR (376 MHz, CDCl3) -65.65 (t, J = 10.8 Hz, 3 F). HRMS (EI): m/z [M]+ calcd for C13H16F3NO: 259.1184; identified: 259.1189 (1.9 ppm). IR (film): 3317, 2978, 2873, 1654, 1599, 1522, 1412, 1315, 1265, 1244, 1138, 1072, 905, 806, 698, 656 cm-1. N,N-Dibenzyl-3-(two,two,2-trifluoroethyl)aniline (2d)–General Process B was followed making use of 1d (115 mg, 0.Buy4-Amino-7-bromoisoindolin-1-one 250 mmol). Workup and chromatographic purification (hexanes/DCM 1:017:3) afforded the title compound as a colorless oil (80.six mg, 91 ). 1H NMR (400 MHz, CDCl3) 7.40 7.33 (m, four H), 7.32 7.25 (m, six H), 7.17 (t, J = 7.PMID:24318587 9 Hz, 1 H), 6.73 (dd, J = eight.four, two.7 Hz, 1 H), 6.70 six.64 (m, two H), 4.68 (s, 4 H), 3.26 (q, J = 11.0 Hz, two H). 13C1H NMR (101 MHz, CDCl3) 149.six, 138.four, 131.2 (q, J = 2.eight Hz), 129.six, 128.eight, 127.1, 126.eight, 126.0 (q, J = 277.0 Hz), 118.6, 114.three, 112.3, 54.three, 40.7 (q, J = 29.five Hz). 19F NMR (376 MHz, CDCl3) -65.68 (t, J = ten.9 Hz, three F). HRMS (EI): m/z [M]+ calcd for C22H20F3N: 355.1548; found: 355.1561 (three.7 ppm). IR (film): 3061, 3030, 2922, 2860, 1605, 1582, 1499, 1452, 1358, 1259, 1132, 1078, 1028, 991, 964, 922, 777, 729, 696 cm-1.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ Org Chem. Author manuscript; available in PMC 2016 August 21.Ambler et al.Page2-Bromo-3,4-dimethoxy-1-(2,two,2-trifluoroethyl)benzene (2e)–General Process C was followed using 1e (101 mg, 0.250 mmol). Workup and chromatographic purification (hexanes/DCM 1:017:three) afforded the title compound as a colorless oil (57.9 mg, 78 ). 1H NMR (400 MHz, CDCl3) 7.10 (d, J = eight.5 Hz, 1 H), six.87 (d, J = eight.6 Hz, 1 H), three.88 (s, 3 H), 3.86 (s, three H), three.60 (q, J = 10.six Hz, 2 H).