Ethyl bromoacetate → HCID 22396717, compound

HRID 2307011Notes

Reaction equation

HRID 2307011 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:12]2[NH:11][C:10]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17][C:9]=3[C:8]=2[CH:7]=[CH:6][C:5]=1[Cl:25].Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29]>CN(C=O)C>[Cl:3][C:4]1[C:12]2[N:11]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:10]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:16][CH2:17][C:9]=3[C:8]=2[CH:7]=[CH:6][C:5]=1[Cl:25]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 22397004HCID 22397004, compound

Product 1

HCID 22396717HCID 22396717, compoundYield 81%

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 7,8-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 2.5 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 1.5 g (81%) of a white solid: mp 132.5-135.0° C.; IR (diffuse reflectance) 2974, 1747, 1683, 1465, 1450, 1416, 1365, 1303, 1255, 1216, 1195, 1170, 1155, 1115, 803 cm−1; MS (EI) m/z 440 (M+), 442, 440, 386, 385, 384, 311, 300, 298, 57, 56; Anal. Calcd for C21H26Cl2N2O4: C, 57.15; H, 5.94; N, 6.35; found: C, 57.13; H, 5.98; N, 6.36.

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl after 2.5 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-79d51f003de94015ab02bf40fd0a071d
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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