(2,4-Dichlorophenyl)hydrazine monohydrochloride → Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

HRID 2427800Notes

Reaction equation

HRID 2427800 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:28][CH:29]=O)[CH:9]([C:13]2[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.Cl.[Cl:32][C:33]1[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=1[NH:40]N>[Cl-].[Cl-].[Zn+2].C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[C:35]3[C:34](=[C:33]([Cl:32])[CH:38]=[C:37]([Cl:39])[CH:36]=3)[NH:40][CH:29]=2)[CH:9]([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:18])=[CH:26][CH:27]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 2723905(2,4-Dichlorophenyl)hydrazine monohydrochlorideHCID 86619550Methyl N-{4-[2-(4-chlorophenyl)-4-oxo-1-propylbutyl]benzoyl}-beta-alaninate

Product 1

HCID 67262870Methyl N-(4-{1-[(4-chlorophenyl)(5,7-dichloro-1H-indol-3-yl)methyl]butyl}benzoyl)-beta-alaninate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

An acetic acid solution (5 ml) containing the intermediate from Step B (200 mg, 0.47 mmol), 2,4-dichlorophenyl hydrazine hydrochloride (120 mg, 0.56 mmol) and ZnCl2 (2.29M in AcOH, 0.61 ml, 1.4 mmol) was heated at 80° C. for 30 minutes. The solution was concentrated and the residue dissolved in EtOAc. The EtOAc solution was washed with water, brine and dried over Na2SO4. The filtered solution was concentrated and the residue purified by silica gel chromatography using a hexanes/EtOAc gradient to give the title compound as a mixture of diastereomers. The mixture was purified further using reverse phase HPLC. The major (and more active) diastereomer, which is also the slower (second) eluting on HPLC, was resolved on a Chiralpak AD-H column (2 cm×25 cm) eluting with 10% EtOH/Heptane at 9 ml/min.

Workup

  1. concentrationThe solution was concentrated
  2. dissolutionthe residue dissolved in EtOAc
  3. washThe EtOAc solution was washed with water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe filtered solution was concentrated
  6. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-bd46fa3f55794610b6b251338cc00117
Source dataset
uspto-grants-2011_06
Patent number
US07968589B2

Reaction notes

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