Sodium hydride → tert-Butyl 9,10-dichloro-6-(2-phenoxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 1356316Notes

Reaction equation

HRID 1356316 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15][C:5]=3[C:4]=2[C:3]=1[Cl:23].[H-].[Na+].Br[CH2:27][CH2:28][O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:27][CH2:28][O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:6]3[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:14][CH2:15][C:5]=3[C:4]=2[C:3]=1[Cl:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68526Benzene, (2-bromoethoxy)-HCID 22396855tert-butyl 9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396602tert-Butyl 9,10-dichloro-6-(2-phenoxyethyl)-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 13.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 9,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.20 g, 0.56 mmol) in DMF (4 mL), sodium hydride (60% dispersion in mineral oil, 34 mg, 0.84 mmol) was added. After 25 min, β-bromophenetole (0.15 mL, 1.1 mmol) was added. The reaction was quenched with saturated aqueous NH4Cl after 2 h and extracted with EtOAc (3×15 mL). The combined organic extracts were washed with brine, dried over Na2SO4, decanted, and concentrated. The crude product was purified by column chromatography (Biotage, 40S) with heptane/EtOAc (17:3) and triturating with hexanes gave 35 mg (13%) of a white solid: mp 175.0-176.0° C.; 1H NMR (400 MHz, DMSO) δ 7.53 (d, J=8.8 Hz, 1H), 7.24 (m, 3H), 6.90 (t, J=7.6 Hz, 1H), 6.81 (d, J=7.6 Hz, 1H), 6.81 (d, J=7.9 Hz, 2H), 4.60 (m, 2H), 4.17 (m, 2H), 3.67 (m, 2H), 3.61 (m, 2H), 3.14 (t, J=5.3 Hz, 2H), 1.41 (s, 9H); IR (diffuse reflectance) 2967, 2931, 1676, 1493, 1448, 1422, 1406, 1363, 1298, 1245, 1221, 1167, 1118, 754, 690 cm−1; MS (EI) m/z 474 (M+), 333, 95, 92, 79, 78, 76, 67, 64, 57, 55; HRMS (FAB) calcd for C25H28Cl2N2O3+H 475.1555, found 475.1559; Anal. Caled for C25H28Cl2N2O3: C, 63.16; H, 5.94; N, 5.89; found: C, 63.47; H, 6.11; N, 5.84.

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl after 2 h
  2. extractionextracted with EtOAc (3×15 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. customdecanted
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (Biotage, 40S) with heptane/EtOAc (17:3)
  8. customtriturating with hexanes

Sources & evidence

ORD record
ord-fc7b9f55ee9b42098a426efbe1bd6017
Source dataset
uspto-grants-2003_07
Patent number
US06586421B2

Reaction notes

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