4-BROMOINDOLE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

Di-tert-butyl dicarbonate (17 g, 76.5 mmol) was added to a solution of 4-Bromoindole 4-1 (10 g, 51 mmol) and DMAP (0.6To a solution of 4-bromoindole (1.96 g, 10 mmol) in dichloromethane (50 mL), DMAP (122 mg, 1 mmol) and di-tert-butyl dicarbonate (2.4 g, 11 mmol) were added, The reaction system is stirred at room temperature for 8 hours.Work-up gave tert-butyl 4-bromo-1H-indol-1-yl carbonate (2.96 g, 99percent yield).BocStep 84a: 73/4rt-butyl 4-bromo-lH-indole-l-carboxylate (Compound 0601-176)The solution of 4-bromoindole (394 mg, 2.00 mmol), (Boc)Step 84a: Tert-butyl 4-bromo-1H-indole-1-carboxylate (Compound 0601-176)[0559]The solution of 4-bromoindole (394 mg, 2.00 mmol), (Boc)MeCN (6 mL) solution of 4-bromo-indole (394mg, 2.00mmol), (Boc) 2O (523mg, 2.40mmol), was DMAP (293mg, 2.4mmol) to a solution of and Et3N (0.4mL) was stirred at room temperature for 2 hours . The solvent was removed and the residue was dissolved in ethyl acetate (40 mL), washed with water (3 × 20 mL) and brine (1X20mL), and the organic layer concentrated, and purified by column chromatography on silica gel (petroleum ether) on, to give compound 0601-176 as a colorless oil (508mg, 85percent).To a solution of 4-bromo-lH-indole (LXXXVII) (10 g, 50.8 mmol, 1 eq), DMAP (622 mg, 5.1 mmol, 0.1 eq) and TEA (10.6 ml, 76.1 mmol, 3 eq) in DCM (200 mL) was added B0C2O (14.4 mL, 61 mmol, 1.2 eq) at 0°C. The reaction was warmed to room temperature and stirred for 2 h. Water (200 mL) was added and the mixture was extracted with DCM twice. The solvent was evaporated under vacuum to give fert-butyl 4-bromo-lH-indole-l-carboxylate (LXXXVIII) as white solid (11.4 g, 38.5 mmol, 76percent yield). NMR (CDC1To a solution of 4-bromo-1H-indole (LXX) (10 g, 50.8 mmol, 1 eq), DMAP (622 mg, 5.1 mmol, 0.1 eq) and TEA (10.6 ml, 76.1 mmol, 3 eq) in DCM (200 mL) was added Boc2O (14.4 mL, 61 mmol, 1.2 eq) at 0°C. The reaction was warmed to room temperature and stirred for 2 h. Water (200 mL) was added and the mixture was extracted with DCM twice. The solvent was evaporated under vacuum to give tert-butyl 4-bromo-1H-indole-1-carboxylate (LXXI) as white solid (11.4 g, 38.5 mmol, 76percent yield). 1H NMR (CDCI3, 400 MHz) δ ppm 1.68 (s, 9H), 6.64 (d, J=4Hz, 1H), 7.17 (t, J=8.4Hz, 1H), 7.39 (d, J=7.6Hz, 1H), 7.64 (d, J=3.2Hz, 1H), 8.11 (d, J=8.0Hz, 1H); ESIMS found for C13H14BrNO2 m/z 297.1 (M+H).To a solution of 4-bromo-1H-indole (LXX) (10 g, 50.8 mmol, 1 eq), DMAP (622 mg, 5.1 mmol, 0.1 eq) and TEA (10.6 ml, 76.1 mmol, 3 eq) in DCM (200 mL) was added Boc2O (14.4 mL, 61 mmol, 1.2 eq) at 0°C. The reaction was warmed to room temperature and stirred for 2 h. Water (200 mL) was added and the mixture was extracted with DCM twice. The solvent was evaporated under vacuum to give tert-butyl 4-bromo- 1H-indole- 1 -carboxylate (LXXI) as white solid (11.4 g, 38.5 mmol, 76percent yield). ‘HNMR(CDC13, 400 MHz) Eppm 1.68 (s, 9H), 6.64 (d, J=4Hz, 1H), 7.17 (t, J=8.4Hz, 1H), 7.39 (d, J=7.6Hz, 1H), 7.64 (d, J=3.2Hz, 1H), 8.11 (d, J8.OHz, 1H); ESIMS found for C, 3H, 4BrNO2 mlz 297.1 (M+H).To a suspension of 60percent NaH (0.449 g, 11.2 mmol) in dry THF (20.0 mL) was added a solution of compound 1 (2.000 g, 10.20 mmol) in THF (20.0 mL) at −78° C. The reaction mixture was stirred for 1 h. A solution of ditertiary butyl dicarbonate (2.58 mL, 11.2 mmol) in THF (20.0 mL) was added to the above solution drop-wise at −78° C. and stirred at rt for 16 h The reaction progress was monitored by diluting an aliquot of the reaction mixture with water and extracting with EtOAc. The organic layer was spotted over an analytical silica gel TLC plate and visualized using 254 nm UV light. The reaction progressed to completion with the formation of a non-polar spot. The RAdd DI-TERT-BUTYL dicarbonate (1.4 g. 6.4 mmol) and sodium hydride (0.15 g, 60percent dispersion in mineral oil, 3.8 mmol) to a solution of 4-bromoindole (0.4 mL, 3.2 mmol) in THF (11 mL) at 0 C. Stir the reaction for 22 h, quench with saturated aqueous ammonium chloride, and extract with methylene chloride. Dry the combined organic extracts with sodium sulfate, filter, and concentrate in vacuo. Purify by flash column chromatography, utilizing the appropriate mixture of hexanes and methylene chloride, to provide 0.85 g (90percent) of the titled compound as a clear, colorless OIL.APOS;H NMR (CDC13) 8 8. 10 (d, J = 8 HZ, 1H), 7.63 (d, J = 4 Hz, 1H), 7. 38 (d, J = 8 HZ, 1H), 7.16 (t, J = 8 Hz, 1H), 6.64 (d, J = 4 Hz, 1H), 1.67 (s, 9H). TLC (SI02) : Rf 0. 3 (9: 1 hexanes/methylene chloride).

Molecular Weight:296.16
XLogP3:4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:295.02079
Monoisotopic Mass:295.02079
Topological Polar Surface Area:31.2
Heavy Atom Count:17
Complexity:300
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes