T.19 Gram-scale Decarboxylative Trifluoromethylation: An oven-dried 25 mL Schlenk flask was sealed using a rubber septum and cooled under an atmosphere of dry N2. CuI (0.23 g, 1.two mmol) was added to 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 with 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 in the reaction; hence, the reaction need to either be conducted inside a pressure-rated vessel, or open to an inert atmosphere). MeCN (three.0 mL), MeO2CCF2Br (0.26 mL, two.four mmol), 1b (two.2 g, six.0 mmol), and DMF (three.0 mL) have been injected into the flask, which was placed within a pre-heated oil bath (70 ) and stirred for 24 h. Just after cooling to room 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 over Na2SO4, filtered, as well as the solvent was removed in vacuo. The residue was purified through silica gel chromatography (hexanes/Et2O 39:1) to provide 2b as a colorless strong (1.four g, 87 ). The 1H and 19F NMR spectrum had been consistent together with the information described above. N-(4-(2,2,2-Trifluoroethyl)phenyl)pivalamide (2c)–General Procedure B was followed working with 1c (91.0 mg, 0.250 mmol). Workup and chromatographic purification (hexanes/EtOAc 1:09:1) afforded the title compound as a colorless solid (52.8 mg, 81 ). mp 13233 . 1H NMR (400 MHz, CDCl3) 7.54 (d, J = eight.4 Hz, 2 H), 7.37 (s, 1 H), 7.25 (d, J = eight.3 Hz, two H), three.33 (q, J = ten.eight Hz, two H), 1.32 (s, 9 H). 13C1H NMR (101 MHz, CDCl3) 176.eight, 138.1, 130.8, 125.9 (q, J = 3.0 Hz), 125.8 (q, J = 276.7 Hz), 120.two, 39.HDAC6 Protein supplier 76, 39.74 (q, J = 29.8 Hz), 27.7. 19F NMR (376 MHz, CDCl3) -65.65 (t, J = ten.8 Hz, three 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-(2,2,2-trifluoroethyl)aniline (2d)–General Process B was followed using 1d (115 mg, 0.250 mmol).GIP, Human (HEK293, hFc, solution) Workup and chromatographic purification (hexanes/DCM 1:017:three) afforded the title compound as a colorless oil (80.PMID:32180353 six mg, 91 ). 1H NMR (400 MHz, CDCl3) 7.40 7.33 (m, 4 H), 7.32 7.25 (m, 6 H), 7.17 (t, J = 7.9 Hz, 1 H), 6.73 (dd, J = eight.4, two.7 Hz, 1 H), six.70 6.64 (m, two H), four.68 (s, four H), three.26 (q, J = 11.0 Hz, 2 H). 13C1H NMR (101 MHz, CDCl3) 149.six, 138.4, 131.2 (q, J = 2.eight Hz), 129.6, 128.8, 127.1, 126.eight, 126.0 (q, J = 277.0 Hz), 118.6, 114.3, 112.three, 54.three, 40.7 (q, J = 29.five Hz). 19F NMR (376 MHz, CDCl3) -65.68 (t, J = 10.9 Hz, 3 F). HRMS (EI): m/z [M]+ calcd for C22H20F3N: 355.1548; found: 355.1561 (3.7 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; out there in PMC 2016 August 21.Ambler et al.Page2-Bromo-3,4-dimethoxy-1-(two,2,2-trifluoroethyl)benzene (2e)–General Procedure C was followed using 1e (101 mg, 0.250 mmol). Workup and chromatographic purification (hexanes/DCM 1:017:3) afforded the title compound as a colorless oil (57.9 mg, 78 ). 1H NMR (400 MHz, CDCl3) 7.10 (d, J = 8.5 Hz, 1 H), six.87 (d, J = 8.6 Hz, 1 H), three.88 (s, three H), 3.86 (s, 3 H), 3.60 (q, J = ten.6 Hz, 2 H).