General Techniques: All Reactions Requiring Anhydrous Conditions Were Conducted in Flame-Dried

SPECIMEN EXPERIMENTAL

General techniques: All reactions requiring anhydrous conditions were conducted in flame-dried glass apparatus under an atmosphere of N2. THF and Et2O were freshly distilled from sodium benzophenone ketyl prior to use. DMSO and DMF were distilled from CaH2 at 15 mmHg. CH2Cl2 was freshly distilled from CaH2 and PhMe was distilled from molten sodium metal. Anhydrous MeOH was obtained by distillation from its magnesium alkoxide and stored under N2 over activated 4Å molecular sieves. Preparative chromatographic separations were performed on EM Science silica gel 60 (35-75 mm) and reactions followed by TLC analysis using Sigma-Aldrich silica gel 60 plates (2-25 mm) with fluorescent indicator (254 nm) and visualized with UV, phosphomolybdic acid or p-anisaldehyde. All commercially available reagents were purchased from Aldrich and were used as received unless otherwise noted.

Melting points were recorded using open capillary tubes on a Griffin melting point apparatus and are uncorrected. Specific optical rotations were measured at ambient temperature (22 °C) from CHCl3 solutions on an Optical Activity AA-1000 polarimeter using a 1 mL cell with 0.2 dm path length. Infra-red spectra were recorded on a Perkin Elmer Spectrum One FT-IR spectrometer using a thin film supported between NaCl plates or KBr discs where stated. 1H and 13C NMR spectra were recorded in Fourier transform mode at the field strength specified on Bruker Avance FT-NMR spectrometers. Spectra were obtained from the specified deuterated solvents in 5 mm diameter tubes. Chemical shift in ppm is quoted relative to residual solvent signals calibrated as follows: CDCl3 dH (CHCl3) = 7.26 ppm, dC = 77.2 ppm; (CD3)2SO dH (CD3SOCHD2) = 2.50 ppm, dC = 39.5 ppm; C6D6 dH (C6HD5) = 7.16 ppm, dC = 128.0 ppm; CD3OD dH (CHD2OD) = 3.31 ppm, dC = 49.0 ppm; (CD3)2CO dH (CD3COCHD2) = 2.05 ppm, dC = 29.8 ppm. Multiplicities in the 1H NMR spectra are described as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad; coupling constants are reported in Hz. Numbers in parentheses following carbon atom chemical shifts refer to the number of attached hydrogen atoms as revealed by the DEPT spectral editing technique. Electron-impact (EI), chemical ionisation (CI), and fast atom bombardment (FAB) mass spectra (MS and HRMS) were obtained with a Micromass VG Autospec spectrometer. Electrospray (ES) mass spectra (MS and HRMS) were obtained with a Micromass LCT spectrometer. Ion mass/charge (m/z) ratios are reported as values in atomic mass units.

Laboratory notebook reference: PRB108.

8-Bromo-7-(dimethylaminocarbonyloxy)quinoline: A solution of i-Pr2NH (2.06 mL, d = 0.722, 1.49 g, 14.8 mmol) in anhydrous THF (20 mL) at –20 °C under N2 was treated dropwise with n-BuLi (9.64 mL, 1.47 M in hexanes, 14.2 mmol) and stirred for 5 min. The resulting solution of LDA was further cooled to –78 °C and 7-(dimethylaminocarbonyloxy)quinoline (2.55 g, 11.8 mmol) in anhydrous THF (15 mL) added carefully over 3 min down the cold flask side-wall. The dark brown solution of lithiated quinoline was stirred for 40 min at –78 °C and then added via cannula over 5 min to a similarly cooled solution of 1,2-dibromotetrachloroethane (7.69 g, 23.6 mmol) in anhydrous THF (30 mL). The cooling bath was removed and the light yellow reaction mixture allowed to stir for 45 min while slowly warming to rt. Sat. aq. NH4Cl (10 mL) was added and the mixture partitioned between EtOAc (20 mL) and H2O (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (10 mL). The combined organic extracts were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. The crude residue (8.21 g) was further purified by column chromatography (eluting with 50-75% EtOAc in hexanes) to yield the bromoquinoline (2.47 g, 8.4 mmol, 71%) as a light yellow solid. A small sample of the material was recrystallised from THF to afford large colourless prisms: mp 122-124 °C (THF); [a]D + 00.0 (c 1.00, CHCl3); IR (neat) 2951, 1709, 1597, 1355, 1048, 980, 949, 856, 826, 743, 667, 642, 568, 510 cm–1; 1H NMR (300 MHz, CDCl3) d 9.05 (1H, dd, J = 4.3, 1.7 Hz), 8.18 (1H, dd, J = 8.2, 1.7 Hz), 7.80 (1H, d, J = 8.8 Hz), 7.49 (1H, d, J = 8.8 Hz), 7.46 (1H, dd, J = 8.2, 4.3 Hz), 3.26 (3H, s), 3.08 (3H, s) ppm; 13C NMR (75 MHz, CDCl3) d 153.7 (0), 151.6 (1), 150.4 (0), 146.3 (0), 136.6 (1), 127.8 (1), 127.3 (0), 123.8 (1), 121.5 (1), 117.5 (0), 37.1 (3), 36.9 (3) ppm; MS (ES) m/z 297 (M+H)+, 295 (M+H)+; HRMS (ES) m/z 295.0078 (calcd. for C12H12Br(79)N2O2: 295.0082); Anal. calcd. for C12H11BrN2O2: C, 48.84; H, 3.76; N, 9.49. Found: C, 48.95; H, 3.75; N, 9.60.