Hydrochloric Acid → Phenylmethyl 6-chlorosalicylate

HRID 1885967Notes

Reaction equation

HRID 1885967 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([OH:11])[C:7]=1[C:8]([OH:10])=[O:9].[H-].[Na+].[H][H].[CH2:16](Cl)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[I-].[Na+].Cl.[Cl-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([OH:11])[C:7]=1[C:8]([O:10][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:9]

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 5238Sodium IodideHCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 925912-Chloro-6-hydroxybenzoic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 18006228Phenylmethyl 6-chlorosalicylateYield 63.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, a solution of 5.7 grams (0.033 mole) of 6-chlorosalicylic acid in 200 mL of dimethylformamide was vigorously stirred, and 1.3 grams (0.033 mole) of 60% sodium hydride in mineral oil was added in one portion. Upon completion of addition, the reaction mixture was stirred for approximately 5 minutes until evolution of hydrogen gas had ceased. After this time 4.2 grams (0.033 mole) of benzyl chloride and 5.0 grams (0.033 mole) of sodium iodide were each added in one portion. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 30 hours. After this time the reaction mixture was poured into a mixture of 150 mL of aqueous 3N hydrochloric acid and 300 mL of an aqueous solution saturated with sodium chloride. The mixture was extracted with three 250 mL portions of diethyl ether. The ether extracts were combined, and the combination was washed with two 250 mL portions of an aqueous solution saturated with sodium chloride. The aqueous washes were combined and extracted with one 250 mL portion of ethyl acetate. The ethyl acetate extract was then washed with three 100 mL portions of an aqueous solution saturated with sodium chloride. The diethyl ether and ethyl acetate extracts were combined and were dried with magnesium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was adsorbed onto silica gel and was subjected to column chromatography. Elution was accomplished with 10% ethyl acetate in heptane. The appropriate fractions were combined and concentrated under reduced pressure to yield 5.5 grams of phenylmethyl 6-chlorosalicylate. The nmr spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. additioneach added in one portion
  3. additionUpon completion of addition
  4. extractionThe mixture was extracted with three 250 mL portions of diethyl ether
  5. washthe combination was washed with two 250 mL portions of an aqueous solution saturated with sodium chloride
  6. extractionextracted with one 250 mL portion of ethyl acetate
  7. extractionThe ethyl acetate extract
  8. washwas then washed with three 100 mL portions of an aqueous solution saturated with sodium chloride
  9. dry with materialwere dried with magnesium sulfate
  10. filtrationThe mixture was filtered
  11. concentrationthe filtrate was concentrated under reduced pressure to a residue
  12. washElution
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-551b063e844c49ddbe7c2a7d946bf958
Source dataset
uspto-grants-1992_09
Patent number
US05149357

Reaction notes

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