Sodium hydride → HCID 22396863, compound

HRID 1071105Notes

Reaction equation

HRID 1071105 reaction equation
[Cl:1][C:2]1[C:3]([Cl:23])=[CH:4][C:5]2[C:6]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11][C:7]=3[NH:8][C:9]=2[CH:10]=1.[H-].[Na+].[F:26][C:27]1[CH:36]=[CH:35][C:30]([O:31][CH2:32][CH2:33]Br)=[CH:29][CH:28]=1>CN(C=O)C>[Cl:1][C:2]1[C:3]([Cl:23])=[CH:4][C:5]2[C:6]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:12][CH2:11][C:7]=3[N:8]([CH2:33][CH2:32][O:31][C:30]3[CH:35]=[CH:36][C:27]([F:26])=[CH:28][CH:29]=3)[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 20641711-(2-Bromoethoxy)-4-fluorobenzeneHCID 22396667HCID 22396667, compound

Product 1

HCID 22396863HCID 22396863, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 8,9-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.40 g, 1.1 mmol) in DMF (5 mL), sodium hydride (60% dispersion in mineral oil, 68 mg, 1.7 mmol) was added. After 25 min, 4-fluorophenoxy ethyl bromide (0.34 mL, 2.3 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, 40M) with heptane/EtOAc (gradient, 9:1 to 17:3) to give 0.43 g (78%) of a white foam: 1H NMR (300 MHz, CDCl3) δ 7.51 (d, J=3.8 Hz, 1H), 7.40 (d, J=6.0 Hz, 1H), 6.92 (t, J=8.7 Hz, 2H), 6.70 (m, 2H), 4.40 (t, J=5.3 Hz, 2H), 4.13 (t, J=5.3 Hz, 4H), 3.69 (m, 4H), 3.08 (m, 2H), 2.90 (m, 2H), 1.48 (s, 9H); IR (diffuse reflectance) 1687, 1505, 1468, 1414, 1366, 1296, 1268, 1248, 1218, 1169, 1114, 1105, 865, 827, 746 cm−1; MS (ES+) m/z 493 (M+H+), 516, 515, 366, 364, 265, 253, 138, 94, 91, 85; Anal. Calcd for C25H27Cl2FN2O3: C, 60.86; H, 5.51; N, 5.68; found: C, 60.91; H, 5.61; N, 5.64.

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, 40M) with heptane/EtOAc (gradient, 9:1 to 17:3)

Sources & evidence

ORD record
ord-3b98b135fdea437c9d26b714cc575554
Source dataset
uspto-grants-2005_06
Patent number
US06903090B2

Reaction notes

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