Ethyl bromoacetate → HCID 22396905, compound

HRID 1370451Notes

Reaction equation

HRID 1370451 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([Cl:25])[C:7]2[C:8]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13][C:9]=3[NH:10][C:11]=2[CH:12]=1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]([Cl:25])[C:7]2[C:8]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:14][CH2:13][C:9]=3[N:10]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:11]=2[CH:12]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 22396843HCID 22396843, compound

Product 1

HCID 22396905HCID 22396905, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 0.25 g, 6.3 mmol) was added to a solution of tert-butyl 8,10-dichloro-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.5 g, 4.2 mmol) in DMF (15 mL). After 20 min, ethyl bromoacetate (0.94 mL, 8.4 mmol) was added. The reaction was quenched with saturated aqueous NH4Cl after 1.5 h and extracted with EtOAc (3×20 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 (3:1) followed by crystallization from MeOH/EtOAc to give 1.4 g (78%) of a white solid: mp 144.5-147.0° C.; IR (diffuse reflectance) 2982, 2972, 1748, 1690, 1456, 1411, 1373, 1366, 1352, 1252, 1222, 1202, 1159, 1115, 824 cm; MS (EI) m/z 440 (M+), 442, 440, 386, 384, 310, 300, 298, 86, 84, 57; Anal. Calcd for C21H26Cl2N2O4: C, 57.15; H, 5.94; N, 6.35; found: C, 57.15; H, 6.04; N, 6.37.

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl after 1.5 h
  2. extractionextracted with EtOAc (3×20 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 (3:1)
  8. customfollowed by crystallization from MeOH/EtOAc

Sources & evidence

ORD record
ord-9775a1cc44c64cbaab0144acdef6a05c
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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