1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamide

HRID 1801574Notes

Reaction equation

HRID 1801574 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([OH:7])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[Cl:33][C:34]1[CH:35]=[C:36]([C@H:40]([NH2:42])[CH3:41])[CH:37]=[CH:38][CH:39]=1>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([NH:42][C@@H:40]([C:36]1[CH:37]=[CH:38][CH:39]=[C:34]([Cl:33])[CH:35]=1)[CH3:41])=[O:7]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2507697(R)-1-(3-chlorophenyl)ethanamineHCID 27355443-Bromo-4-chlorobenzoic acid

Product 1

HCID 59803174(R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamideYield 99.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-4-chlorobenzoic acid 31 (4.209 g, 17.9 mmol) in DMF (40 mL) at room temperature was added HOBT (3.31 g, 21.6 mmol) and EDCI (4.13 g, 21.5 mmol). The solution was stirred for 15 min and (R)-1-(3-chlorophenyl)ethanamine (2.92 g, 18.8 mmol) was added. The reaction mixture was stirred at room temperature for 14 h and diluted with EtOAc. The aqueous phase was extracted with EtOAc (1×), and the combined organic extracts were washed with water (2×), brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 20% to 40% EtOAc in hexanes) gave (R)-3-bromo-4-chloro-N-(1-(3-chlorophenyl)ethyl)benzamide 32 (6.659 g, 99.9% yield) as a white solid. Mass spectrum: calculated for C15H12BrCl2NO 371.0. found 372.0 (M++1).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 14 h
  2. extractionThe aqueous phase was extracted with EtOAc (1×)
  3. washthe combined organic extracts were washed with water (2×), brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography on silica gel (eluted with 20% to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-38ef82ce54214086bb39af890e917706
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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