Hydrochloric Acid → 2-chloro-3,4,5-trimethoxybenzoic Acid

HRID 2230592Notes

Reaction equation

HRID 2230592 reaction equation
N[C:2]1[C:11]([O:12][CH3:13])=[C:10]([O:14][CH3:15])[C:9]([O:16][CH3:17])=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[ClH:18].O1CCOCC1.N([O-])=O.[Na+]>C(OCC)(=O)C.[Cu]Cl.ClCCl>[Cl:18][C:2]1[C:11]([O:12][CH3:13])=[C:10]([O:14][CH3:15])[C:9]([O:16][CH3:17])=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 78735Methyl 3,4,5-trimethoxyanthranilateHCID 23668193Sodium Nitrite

Product 1

HCID 184647142-chloro-3,4,5-trimethoxybenzoic Acid

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combine methyl 2-amino-3,4,5-trimethoxybenzoate (4.8 g, 20 mmol) and dichloromethane (20 mL). Cool in an ice bath. Add a solution of hydrochloric acid in dioxane (10 mL, 4 M, 40 mmol). Add polyethylene glycol 200 (20 mL) followed by sodium nitrite (2.76 g, 40 mmol). After 10 minutes add copper (I) chloride (3.96 g, 40 mmol). Warm to ambient temperature. After 18 hours, dilute the reaction mixture with ethyl acetate and extract with a 1 M aqueous solution of sodium hydroxide an then brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. the title compound. Chromatograph the residue on silica gel eluting sequentially with hexane and then 5% ethyl acetate/hexane to give methyl 2-chloro-3,4,5-trimethoxybenzoate: Rf=0.7 (silica gel, 20% ethyl acetate/toluene).

Workup

  1. temperatureCool in an ice bath
  2. extractionextract with a 1 M aqueous solution of sodium hydroxide an then brine
  3. dry with materialDry the organic layer over MgSO4
  4. filtrationfilter
  5. customevaporate in vacuo
  6. customto give a residue

Sources & evidence

ORD record
ord-3d3086d7361b4825b322bcf736464272
Source dataset
uspto-grants-2002_07
Patent number
US06423704B1

Reaction notes

Loading…