Oxalyl chloride → 3-bromo-N-cyclopropyl-4-methylbenzamide

HRID 1765804Notes

Reaction equation

HRID 1765804 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[CH:18]1([NH2:21])[CH2:20][CH2:19]1>C1C=CC=CC=1.ClCCl.CN(C)C=O.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([NH:21][CH:18]1[CH2:20][CH2:19]1)=[O:7]

Participants

8

Reactant 3

HCID 65578Oxalyl chlorideHCID 69828CyclopropylamineHCID 821303-Bromo-4-methylbenzoic acid

Product 1

HCID 211071523-bromo-N-cyclopropyl-4-methylbenzamide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 241BenzeneSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A stirred, cooled (ice bath) solution of 3-bromo-4-methyl-benzoic acid (Aldrich, 5 g, 23.25 mmol) in benzene (50 mL), dichloromethane (10 mL) and N,N-dimethylformamide (0.5 mL) was treated with oxalyl chloride (4 mL, 46.5 mmol). The reaction mixture was allowed to warm to ambient temperature over 3 h. The volatiles were then distilled off in vacuo, the residue was diluted with anhydrous dichloromethane (50 mL) under argon, cooled (ice bath) and treated with 4-(dimethylamino)pyridine (5.67 g, 46.5 mmol) followed by cyclopropyl amine (1.93 mL, 27.9 mmol). After 3 h, the reaction mixture was diluted with dichloromethane and washed with water. The organic phase was dried-over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford the title product that was used as such for the next step (6.0 g,˜100%).

Workup

  1. distillationThe volatiles were then distilled off in vacuo
  2. additionthe residue was diluted with anhydrous dichloromethane (50 mL) under argon
  3. temperaturecooled (ice bath)
  4. washwashed with water
  5. filtrationfiltered
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-23927d08b2ed42629b68dd3b09d2c3eb
Source dataset
uspto-grants-2007_06
Patent number
US07226951B2

Reaction notes

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