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

HRID 5376

Reaction equation

HRID 5376 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%

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 mmoles) 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° C. for 18 hours. The solution is cooled, concentrated in vacuo, and added to water (25 mL). The aqueous solution is extracted with ether, and the extract is 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 is concentrated, diluted with water to 75 mL total volume, extracted with ether, and acidified to pH 3 with concentrated HCl. The precipitate is filtered, washed with water, air dried, and recrystallized from ethyl acetate to afford 0.74 g (57%) of product as fine voluminous white needles, mp 137.5°-139.5° C.

Workup

  1. temperatureA cooled
  2. temperatureheated to 100° C. for 18 hours
  3. temperatureThe solution is cooled
  4. concentrationconcentrated in vacuo
  5. additionadded to water (25 mL)
  6. extractionThe aqueous solution is extracted with ether
  7. dry with materialthe extract is dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. additiontreated with potassium hydroxide (5.0 g)
  10. temperaturerefluxed for one hour
  11. concentrationThe mixture is concentrated
  12. additiondiluted with water to 75 mL total volume
  13. extractionextracted with ether
  14. filtrationThe precipitate is filtered
  15. washwashed with water, air
  16. customdried
  17. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-4a61892e548641678c1f2f77ac5daff8
Source dataset
uspto-grants-1993_09
Patent number
US05244907

Linked notes

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