Dimethylformamide → 4-Chloro-2-(bromoacetamido)benzoic Acid

HRID 582658Notes

Reaction equation

HRID 582658 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].CN(C=O)C.O1CCOCC1.[Br:23][CH2:24][C:25](Br)=[O:26]>O>[Cl:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([NH:1][C:25](=[O:26])[CH2:24][Br:23])[CH:10]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 312751,4-DioxaneHCID 61147Bromoacetyl bromideHCID 666462-Amino-4-chlorobenzoic acid

Product 1

HCID 108036144-Chloro-2-(bromoacetamido)benzoic AcidYield 54%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 2-amino-4-chlorobenzoic acid (10 g, 0.06 mol), anhydrous DMF (30 mL) and anhydrous dioxane was cooled to 0° C. in 300 mL 3-necked flask fitted with magnetic stirrer and constant additional funnel. Bromoacetyl bromide was added dropwise over a 2 h period, keeping the internal temperature between 0-2° C. After the addition was completed, the solution was allowed to warm to room temperature and the reaction mixture was stirred 20 h. The reaction mixture was cooled in an ice-bath and slowly diluted with water (300 mL). The resulting white crystalline product was filtered. Recrystallization from EtOAc/Hex afforded 9.2 g (54%) of the title compound, mp 156.4-158° C.; 1H NMR (DMSO-d6) δ 13.99 (s, 1H, NH), 11.72 (s, 1H, COOH), 8.54 (d, 1H, J=2.0), 8.00 (d, 1H, J=8.8), 7.27 (dd, 1H, J=2.4, J=6.4), 4.28 (s, 2H) 13C NMR (DMSO-d6) δ 168.60, 165.54, 141.12, 138.51, 133.88, 123.36, 119.23, 115.58, 30.54; MS (EI, m/z) 293 (M+).

Workup

  1. customfitted with magnetic stirrer and constant additional funnel
  2. custombetween 0-2° C
  3. additionAfter the addition
  4. temperatureThe reaction mixture was cooled in an ice-bath
  5. filtrationThe resulting white crystalline product was filtered
  6. customRecrystallization from EtOAc/Hex

Sources & evidence

ORD record
ord-7c7bd49e185248b780ce1344ea7bda9f
Source dataset
uspto-grants-1999_07
Patent number
US05925647

Reaction notes

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