Dimethyl malonate → 1-(4-Amino-2-chlorophenyl)ethan-1-one

HRID 333831Notes

Reaction equation

HRID 333831 reaction equation
[Cl-].[NH4+].[Cl:3][C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[C:13](=[O:15])[CH3:14].ClC1C=C([N+]([O-])=O)C=CC=1C(Cl)=O.COC(=O)CC(OC)=O>C(O)C.[Fe].C(Cl)Cl.O>[NH2:10][C:8]1[CH:7]=[CH:6][C:5]([C:13](=[O:15])[CH3:14])=[C:4]([Cl:3])[CH:9]=1

Participants

9

Reactant 4

HCID 7943Dimethyl malonateHCID 25517Ammonium ChlorideHCID 81522Benzoyl chloride, 2-chloro-4-nitro-HCID 3143021-(2-chloro-4-nitrophenyl)ethanone

Product 1

HCID 127338371-(4-Amino-2-chlorophenyl)ethan-1-one

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Iron (2.7 g), ammonium chloride (2.6 g) and water (8.1 ml) were added to a solution of 1-(2-chloro-4-nitro-phenyl)-ethanone ([CAS Reg. No. 67818-41-1], 960 mg) in ethanol (68 ml), which was made from 2-chloro-4-nitro-benzoyl chloride and malonic acid dimethyl ester according to a procedure from Dai et al.; J. Med. Chem. 2005, 48, 6066. The mixture was heated 1 h under reflux. DCM (35 ml) was added, stirred for 2 min and filtered over Celite. The residue was washed with DCM (50 ml). Water (100 ml) was added to the combined organic layers, and then extracted with DCM. The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give the title compound (837 mg) as light yellow oil, which was used in the next step without further purification. MS (m/e)=170.1 [M+H+].

Workup

  1. temperatureThe mixture was heated 1 h
  2. temperatureunder reflux
  3. filtrationfiltered over Celite
  4. washThe residue was washed with DCM (50 ml)
  5. additionWater (100 ml) was added to the combined organic layers
  6. extractionextracted with DCM
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4455f5f37b494753ae403c4a4a44558f
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

Loading…