Page 17 of 24
The Journal of Organic Chemistry
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followed using 2a (69.7 mg, 0.40 mmol), 11 (122.9 mg, 0.44 mmol), LiCl in THF (160 µL, 0.040 mmol), Et3N (111
µL, 0.80 mmol), and CDMT (77.2 mg, 0.44 mmol) in MeCN (1.3 mL) for the first step (4 h) followed by TFA (153
µL, 2.00 mmol) for the second step (room temperature). Column chromatography (silica gel, hexane/acetone = 9:1)
afforded a white solid (152.0 mg, 93%). Mp: 70.5–72.5 ℃. 1H-NMR (400 MHz, CDCl3): δ 10.00 (s, 1H), 7.53–7.50
(m, 2H), 7.22–7.18 (m, 2H), 7.11–7.05 (m, 3H), 6.87 (dd, J = 6.9, 6.9 Hz, 1H), 6.78 (d, J = 7.8 Hz, 1H), 5.53 (s, 1H),
4.30–4.06 (m, 4H), 3.85–3.81 (m, 2H), 3.32 (dd, J = 15.8, 2.5 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H), 1.16 (t, J = 7.2 Hz,
3H); 13C{1H}-NMR (100 MHz, CDCl3): δ 169.2, 168.6, 157.4, 136.6, 131.0, 130.1, 128.7, 126.9, 123.5, 122.2,
119.68, 119.67, 118.4, 117.9, 111.1, 105.9, 66.8, 62.8, 62.5, 55.6, 26.8, 14.08, 14.05; IR (KBr): 3443, 3305, 2983,
1736, 1491, 1454, 1315, 1248, 1198, 752; HRMS (ESI-TOF): Calcd for C23H24N2NaO5 [M + Na]+: 431.1583; Found:
431.1570; Anal. Calcd for C23H24N2O5: C, 67.63; H, 5.92; N, 6.86. Found: C, 67.56; H, 5.82; N, 6.83.
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Diethyl 6-chloro-1-(2-hydroxyphenyl)-1,2,4,9-tetrahydro-3H-pyrido[3,4-b]indole-3,3-dicarboxylate (12b). GP-
3 was followed using 2b (41.7 mg, 0.20 mmol), 11 (61.4 mg, 0.22 mmol), LiCl in THF (80 µL, 0.020 mmol), Et3N
(56 µL, 0.40 mmol), and CDMT (38.6 mg, 0.22 mmol) in MeCN (0.7 mL) for the first step (5 h) followed by TFA
(153 µL, 2.00 mmol) for the second step (50 °C). The residue was purified by column chromatography (silica gel,
hexane/acetone = 9:1 to 7:3) and recycling preparative HPLC to afford a white solid (67.5 mg, 76%). Mp: 79.5–81.5
℃. 1H-NMR (400 MHz, CDCl3): δ 9.87 (s, 1H), 7.49 (s, 1H), 7.41 (s, 1H), 7.29–7.25 (m, 2H), 7.09–7.04 (m, 2H),
6.94 (ddd, J = 7.4, 7.4, 1.2 Hz, 1H), 6.84 (d, J = 7.8 Hz, 1H), 5.51 (s, 1H), 4.37–4.10 (m, 4H), 3.82–3.75 (m, 2H),
3.27 (dd, J = 16.0, 2.8 Hz, 1H), 1.34 (t, J = 7.1 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13C{1H}-NMR (100 MHz, CDCl3):
δ 169.1, 168.4, 157.5, 134.9, 132.6, 130.4, 128.7, 128.1, 125.6, 123.2, 122.6, 119.9, 118.2, 112.1, 106.0, 66.8, 63.0,
62.7, 55.6, 26.6, 14.18, 14.17; IR (KBr): 3410, 3311, 2935, 2900, 2862, 1736, 1718, 1491, 1471, 1444, 1278, 1196,
1043, 1003, 858, 752; HRMS (ESI-TOF): Calcd for C23H23ClN2NaO5 [M + Na]+: 465.1193; Found: 465.1171; Anal.
Calcd for C23H23ClN2O5: C, 62.37; H, 5.23; N, 6.33. Found: C, 62.18; H, 5.18; N, 6.20.
Diethyl
7-(benzyloxy)-1-(2-hydroxyphenyl)-1,2,4,9-tetrahydro-3H-pyrido[3,4-b]indole-3,3-dicarboxylate
(12d). GP-3 was followed using 2d (52.1 mg, 0.19 mmol), 11 (57.2 mg, 0.21 mmol), LiCl in THF (76 µL, 0.019
mmol), Et3N (52 µL, 0.37 mmol), and CDMT (36.0 mg, 0.21 mmol) in MeCN (0.6 mL) for the first step (3 h)
followed by TFA (71 µL, 0.93 mmol) for the second step (room temperature). The residue was purified by column
chromatography (silica gel, hexane/acetone = 9:1 to 7:3) and recycling preparative HPLC to afford a white solid
(74.8 mg, 78%). Mp: 195–196 ℃. 1H-NMR (400 MHz, CDCl3): δ 9.98 (s, 1H), 7.42–7.22 (m, 9H), 6.92 (dd, J = 7.3,
7.3 Hz, 1H), 6.85–6.82 (m, 2H), 6.73 (d, J = 1.8 Hz, 1H), 5.50 (s, 1H), 5.04 (s, 2H), 4.36–4.09 (m, 4H), 3.80–3.77
(m, 2H), 3.28 (dd, J = 16.0, 2.3 Hz, 1H), 1.34 (t, J = 7.1 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H); 13C{1H}-NMR (100 MHz,
CDCl3): δ 169.3, 168.6, 157.6, 155.8, 137.5, 137.3, 130.2, 129.9, 128.68, 128.65, 127.9, 127.5, 123.6, 121.7, 119.7,
119.1, 118.1, 110.3, 106.0, 96.5, 70.7, 66.9, 62.9, 62.6, 55.7, 26.8, 14.19, 14.16; IR (KBr): 3419, 3305, 2983, 2906,
2868, 1732, 1701, 1541, 1508, 1493, 1473, 1458, 1271, 1205, 1155, 754; HRMS (ESI-TOF): Calcd for
C30H30N2NaO6 [M + Na]+: 537.2002; Found: 537.1979; Anal. Calcd for C30H30N2O6: C, 70.02; H, 5.88; N, 5.44.
Found: C, 69.77; H, 5.80; N, 5.46.
Diethyl 1-(2-hydroxyphenyl)-6-methoxy-1,2,4,9-tetrahydro-3H-pyrido[3,4-b]indole-3,3-dicarboxylate (12e).
GP-3 was followed using 2e (40.9 mg, 0.20 mmol), 11 (61.4 mg, 0.22 mmol), LiCl in THF (80 µL, 0.020 mmol),
Et3N (56 µL, 0.40 mmol), and CDMT (38.6 mg, 0.22 mmol) in MeCN (0.7 mL) for the first step (1.5 h) followed by
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