Benzyl 2-bromo-2,2-difluoroacetate (1m)–General Procedure A was followed working with (3-(hydroxylmethyl)phenyl)(phenyl)methanone. Workup and chromatographic purification (hexanes/EtOAc, 1:021:4) afforded the title compound as a pale yellow oil (1.6 g, 88 ). 1H NMR (400 MHz, CDCl3) 7.88 7.77 (m, four H), 7.67 7.59 (m, 2 H), 7.58 7.47 (m, three H), five.43 (s, 2 H). 13C1H NMR (101 MHz, CDCl3) 196.1, 159.4 (t, J = 31.5 Hz), 138.three, 137.3, 133.9, 132.9, 132.three, 130.9, 130.two, 130.0, 129.1, 128.five, 108.7 (t, J = 314.3 Hz), 69.2. 19F NMR (376 MHz, CDCl3) -60.81 (s, two F). HRMS (APCI exane/PhMe): m/z [M+H]+ calcd for C16H12BrF2O3: 368.9938; found: 368.9936 (0.5 ppm). IR (film): 3065, 3040, 2964, 1778, 1585, 1489, 1448, 1377, 1301, 1259, 1213, 1173, 1122, 945, 874, 847, 777, 692, 604 cm-1. Methyl 4-((2-bromo-2,2-difluoroacetoxy)methyl)benzoate (1n)–General Process A was followed applying methyl 4-(hydroxymethyl) benzoate (0.55 g, 3.three mmol). Workup and chromatographic purification (hexanes/EtOAc, 1:019:1) afforded the title compound as a colorless oil (0.91 g, 85 ). 1H NMR (400 MHz, CDCl3) eight.08 (d, J = 7.9 Hz, two H), 7.47 (d, J = 8.0 Hz, two H), five.41 (s, 2 H), three.94 (s, 3 H). 13C1H NMR (101 MHz, CDCl3) 166.6, 159.four (t, J = 31.7 Hz), 138.three, 130.9, 130.two, 128.1, 108.six (t, J = 314.two Hz), 68.9, 52.4. 19F NMR (376 MHz, CDCl3) -60.86 (s, 2 F). HRMS (APCI exane/PhMe): m/z [M]+ calcd for C11H9BrF2O4: 321.9652; found: 321.9639 (four.0 ppm). IR (film): 2955, 1778, 1724, 1616, 1437, 1379, 1283, 1171, 1111, 1020, 955, 847, 756, 708, 602 cm-1. Tert-butyl 3-((2-bromo-2,2-difluoroacetoxy)methyl)-1H-indole-1-carboxylate (1o)–General Process A was followed employing tert-butyl 3-(hydroxymethyl)-1H-indole-1carboxylate (1.2 g, three.0 mmol). Workup and chromatographic purification (hexanes/EtOAc, 1:09:1) afforded the title compound as a colorless solid (0.91 g, 85 ). mp 479 . 1H NMR (400 MHz, CDCl3) 8.18 (d, J = eight.three Hz, 1 H), 7.77 (s, 1 H), 7.64 (dt, J = 7.8, 1.0 Hz, 1 H), 7.39 (ddd, J = eight.5, 7.2, 1.3 Hz, 1 H), 7.31 (td, J = 7.six, 1.1 Hz, 1 H), 5.54 (d, J = 0.7 Hz, 2 H), 1.69 (s, 9 H). 13C1H NMR (126 MHz, CDCl3) 159.7 (t, J = 31.five Hz), 149.five, 135.7, 128.9, 127.1, 125.two, 123.three, 119.2, 115.6, 113.three, 108.8 (t, J = 314.5 Hz), 84.5, 62.0, 28.3. 19F NMR (376 MHz, CDCl3) -60.7 (s, 2 F). HRMS (APCI exane/PhMe): m/z [M]+ calcd for C16H16BrF2NO4: 403.0231; identified: 403.0222 (two.two ppm). IR (film): 3126, 3055, 2980, 2934, 1774, 1736, 1610, 1597, 1572, 1452, 1389, 1371, 1358, 1292, 1273, 1259, 1231, 1159, 1128, 1092, 1020, 945, 854, 768, 746, 704 cm-1. (1-Phenyl-1H-pyrazol-4-yl)methyl 2-bromo-2,2-difluoroacetate (1p)–General Process A was followed making use of (1-phenyl-1H-pyrazol-4-yl)methanol16 (0.1623432-63-2 Purity 87 g, five.744253-37-0 custom synthesis 0 mmol).PMID:23341580 Workup and chromatographic purification (hexanes/EtOAc, 1:04:1) afforded the title compound as a colorless solid (1.5 g, 89 ). mp 601 . 1H NMR (400 MHz, CDCl3) eight.07 (s, 1 H), 7.81 (s, 1 H), 7.71 7.66 (m, 2 H), 7.51 7.44 (m, 2 H), 7.36 7.30 (m, 1 H), five.36 (s, 2 H). 13C1H NMR (101 MHz, CDCl3) 159.7 (t, J = 31.7 Hz), 141.7, 139.8, 129.7, 128.2, 127.2, 119.5, 116.0, 108.9 (t, J = 314.five Hz), 61.0. 19F NMR (376 MHz,Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ Org Chem. Author manuscript; accessible in PMC 2016 August 21.Ambler et al.PageCDCl3) -60.90 (s, two F). HRMS (ESI): m/z [M + H]+ calcd for C12H10BrF2N2O2: 330.9781; discovered: 330.9788 (two.1 ppm). IR (film): 3057, 2970, 1774, 1514, 1489, 1375, 1292, 11689, 1122, 1067, 943, 887, 842, 771, 736, 692, 660 cm-1. (2-Ph.