2-Chloroethyl methyl sulfide → 4-Amino-5-chloro-2-[2-(methylthio)ethoxy]benzoic acid

HRID 2254608Notes

Reaction equation

HRID 2254608 reaction equation
[H-].[Na+].[NH2:3][C:4]1[C:12]([Cl:13])=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[C:6]([OH:14])[CH:5]=1.Cl[CH2:16][CH2:17][S:18][CH3:19]>CN(C)C=O>[NH2:3][C:4]1[C:12]([Cl:13])=[CH:11][C:7]([C:8]([OH:10])=[O:9])=[C:6]([O:14][CH2:16][CH2:17][S:18][CH3:19])[CH:5]=1

Participants

5

Reactant 3

HCID 109652-Chloroethyl methyl sulfideHCID 24758Sodium hydrideHCID 148832224-Amino-5-chloro-2-hydroxybenzoic acid

Product 1

HCID 191084054-Amino-5-chloro-2-[2-(methylthio)ethoxy]benzoic acidYield 57.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A cooled (5° C.) suspension of 60% sodium hydride oil dispersion (0.52 g, 13 mmole) in anhydrous dimethylformamide (15 ml) under nitrogen was treated in portions with 4-amino-5-chloro-2-hydroxybenzoic acid (0.94 g, 5 mmoles) stirred for 15 minutes at 25° C., treated with (2-chloroethyl)methyl sulfide (1.66 g, 15 mmoles), and heated to 100°±5° C. for 18 hours. The solution was cooled, concentrated in vacuo to remove most of the dimethylformamide and water (25 ml) was added. The aqueous solution was extracted with ether (2×25 ml), and the combined extracts were dried (MgSO4), concentrated in vacuo, taken up in 50% aqueous ethanol (50 ml), treated with potassium hydroxide (5.0 g), and refluxed for one hour. The mixture was concentrated to remove most of the ethanol, diluted with water to 75 ml total volume, extracted with ether (2×35 ml), and acidified to pH 3 with concentrated HCl. The resultant precipitate was filtered, washed with water, air dried, and recrystallized from ethyl acetate to yield 0.75 g (57%) of fine voluminous white needles, mp 137.5°-139.5° C.

Workup

  1. temperatureA cooled
  2. temperatureheated to 100°±5° C. for 18 hours
  3. temperatureThe solution was cooled
  4. concentrationconcentrated in vacuo
  5. customto remove most of the dimethylformamide and water (25 ml)
  6. additionwas added
  7. extractionThe aqueous solution was extracted with ether (2×25 ml)
  8. dry with materialthe combined extracts were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. additiontreated with potassium hydroxide (5.0 g)
  11. temperaturerefluxed for one hour
  12. concentrationThe mixture was concentrated
  13. customto remove most of the ethanol
  14. additiondiluted with water to 75 ml total volume
  15. extractionextracted with ether (2×35 ml)
  16. filtrationThe resultant precipitate was filtered
  17. washwashed with water, air
  18. customdried
  19. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-e3a65123518c4a259e8fbe2e7c70db69
Source dataset
uspto-grants-1993_08
Patent number
US05236931

Reaction notes

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