DRL publication No 427.
19c
General Procedure for the Preparation of 2-Substituted Indoles(4): A mixture of 1e (1.60 mmol), 10% Pd/C (51 mg, 0.05 mmol), PPh3 (50 mg, 0.19 mmol), CuI (18 mg, 0.09 mmol) and 2-aminoethanol (4.83 mmol) in H2O (8 mL) was stirred at 25 °C for 1 h under nitrogen. The acetylenic compound 2 (4.00-5.00 mmol) was added slowly to the mixture with stirring. The reaction mixture was then stirred at 80 °C for the time indicated in Table
[1]
. The mixture was cooled to r.t., diluted with EtOAc (120 mL) and filtered through celite. The filtrate was collected, washed with cold H2O (2 × 75 mL), dried over Na2SO4, filtered and concentrated under vacuum. The residue thus obtained was purified by column chromatography (hexane-EtOAc) to afford the desired product.
Spectral and analytical data for 4a: light brown solid; yield 70%; mp 128-130 °C (hexane). 1H NMR (200 MHz, CDCl3): δ = 7.98 (d, J = 8.4 Hz, 1 H), 7.54 (d, J = 2.5 Hz, 1 H), 7.43-7.38 (m, 5 H), 7.19 (d, J = 8.4 Hz, 1 H), 6.65 (s, 1 H), 2.69 (s, 3 H, SO2CH3), 2.46 (s, 3 H, CH3). MS (CI):
m/z = 286 (100) [M + 1]. IR (neat): 1586.1, 1462.5, 1361.1 cm-1. 13C NMR (50 MHz, CDCl3): δ = 142.08, 136.24, 134.20, 131.99, 130.55, 129.96 (2 C), 128.68, 127.60 (2 C), 126.39, 120.88, 115.50, 112.98, 38.91 (SO2CH3), 21.18 (CH3). HPLC: 97.3% [Symmetry Shield RP18 (250 × 4.6 mm), 0.01 M KH2PO4:MeCN, 1 mL/min 225 nm, retention time 13.7 min]. Elemental analysis found C, 67.39; H, 5.35; N, 4.89; C16H15NO2S requires C, 67.34; H, 5.30; N. 4.91%.
Compound 4g: light brown solid; yield 80%; mp 78-80 °C (hexane). 1H NMR (200 MHz, CDCl3): δ = 7.89 (d, J = 8.7 Hz, 1 H), 7.34 (s, 1 H), 7.15 (d, J = 8.4 Hz, 1 H), 6.62 (s, 1 H), 5.02 (d, J = 7.9 Hz, 1 H), 3.09 (s, 3 H), 2.94 (d, J = 5.9 Hz, D2O exchangeable, OH), 2.43 (s, 3 H), 2.07-1.97 (m, 2 H), 1.09 (t, J = 7.3 Hz, 3 H). MS (CI): m/z = 250 (100) [M+ - OH]. IR (neat): 3540.1, 1462.4, 1358.0, 1159.6 cm-1. 13C NMR (50 MHz, CDCl3): δ = 143.42, 135.06, 133.29, 129.16, 126.19, 121.01, 113.67, 108.36, 67.76 (CHOH), 40.12 (SO2CH3), 28.59 (CH2), 20.98 (CH3), 10.53 (CH3). HPLC: 99.3% [Inertsil ODS 3V (250 × 4.6 mm), 0.01 M KH2PO4 in MeCN, 1 mL/min, 220 nm, retention time 16.6 min]. Elemental analysis found C, 58.38; H, 6.40; N, 5.27; C13H17NO3S requires C, 58.40; H, 6.41; N. 5.24%.
