E in PMC 2016 August 21.Ambler et al.Pageused as ionization solvent. Melting points were uncorrected and measured on a Thomas Hoover Capillary Melting Point Apparatus. Basic Process A HO2CCF2Br (1.45 equiv) was added to a round-bottom flask, which was sealed using a rubber septum and attached to an oil bubbler. DCM and DMF had been injected, plus the answer was cooled to 0 . Oxalyl chloride (1.4 equiv) was injected (caution: evolution of noxious gas), and right after five min, the mixture was allowed to warm to rt. Soon after 2 h, the mixture was cooled to 0 , as well as a remedy of benzylic alcohol (1.0 equiv) and NEt3 (two equiv) in DCM was added. The reaction was monitored by TLC analysis, and just after consumption in the benzylic alcohol (generally within 1 h), the reaction was quenched with water, and also the aqueous layer was extracted with DCM or EtOAc (4x). The combined organic layers had been washed with brine, dried more than Na2SO4, and filtered. Immediately after the removal of solvent, the residue was purified by flash column chromatography to afford bromodifluoroacetates 1a . 4-Methylbenzyl 2-bromo-2,2-difluoroacetate (1a)–General Procedure A was followed making use of 4-methylbenzyl alcohol (1.5 g, 12 mmol). Workup and chromatographic purification (hexanes) afforded the title compound as a colorless oil (two.9 g, 87 ). 1H NMR (400 MHz, CDCl3) 7.31 (d, J = 8.0 Hz, two H), 7.22 (d, J = 7.9 Hz, 2 H), five.33 (s, 2 H), two.38 (s, 3 H). 19F NMR (376 MHz, CDCl3) -60.72 (s, two F). Spectroscopic information are constant with all the preceding report.5f 4-(Benzyloxy)benzyl 2-bromo-2,2-difluoroacetate (1b)–General Procedure A was followed employing 4-(benzyloxy)benzyl alcohol (0.751470-47-0 custom synthesis 65 g, 3.0 mmol). Workup and chromatographic purification (hexanes/EtOAc, 1:019:1) afforded the title compound as a colorless solid (0.88 g, 79 ). mp 645 . 1H NMR (400 MHz, CDCl3) 7.51.31 (m, 7 H), 7.01 (d, J = 8.four Hz, two H), 5.31 (s, 2 H), five.10 (s, two H). 13C1H NMR (101 MHz, CDCl3) 159.7, 159.six (t, J = 31.6 Hz), 136.7, 130.8, 128.8, 128.3, 127.6, 125.9, 115.two, 108.9 (t, J = 314.five Hz), 70.2, 69.9. 19F NMR (376 MHz, CDCl3) -60.7 (s, 2 F). HRMS (EI): m/z [M]+ calcd for C16H13BrF2O3: 370.Bromo-PEG2-C2-acid web 0016; located: 370.PMID:23558135 0012 (1.1 ppm). IR (film): 2945, 2866, 1769, 1609, 1585, 1518, 1454, 1302, 1246, 1161, 1126, 1018, 955, 870, 814, 742, 706, 613 cm-1. 4-Pivalamidobenzyl 2-bromo-2,2-difluoroacetate (1c)–General Procedure A was followed using N-[4-(hydroxymethyl)phenyl] pivalamide (0.83 g, 4.0 mmol). Workup and chromatographic purification (hexanes/EtOAc, 1:025:4) afforded the title compound as a yellow strong (1.two g, 85 ). mp 867 . 1H NMR (400 MHz, CDCl3) 7.61.56 (m, 2 H), 7.42 (s, 1 H), 7.39.34 (m, 2 H), five.31 (s, 2 H), 1.32 (s, 9 H). 13C1H NMR (101 MHz, CDCl3) 176.9, 159.5 (t, J = 31.four Hz), 139.1, 129.9, 129.1, 120.two, 108.8 (t, J = 314.3 Hz), 69.6, 39.eight, 27.7. 19F NMR (376 MHz, CDCl3) -60.8 (s, 2 F). HRMS (APCI exane/ PhMe): m/z [M+H]+ calcd for C14H17BrF2NO3: 364.0360; discovered: 364.0362 (0.5 ppm). IR (film): 3292, 2975, 1771, 1655, 1599, 1520, 1460, 1294, 1157, 955, 820, 700, 604 cm-1. 3-(Dibenzylamino)benzyl 2-bromo-2,2-difluoroacetate (1d)–General Procedure A was followed employing [3-(dibenzylamino)phenyl]methanol (0.83 g, 4.0 mmol). Workup andAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptJ Org Chem. Author manuscript; out there in PMC 2016 August 21.Ambler et al.Pagechromatographic purification (hexanes/EtOAc, 1:021:four) afforded the title compound as a yellow solid (1.2 g, 85 ). mp 678 . 1H NMR (400 MHz, CDCl3) 7.41.3.
