Ethanol → 2-(2-(O-tolylamino)benzo[d]oxazol-6-yl)acetic acid

HRID 1883710Notes

Reaction equation

HRID 1883710 reaction equation
[C:1]1([CH3:34])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18](NC3C=C4C(=CC=3)C(CC(O)=O)CC4)=[O:19])[CH:14]=[CH:13][C:11]=2[N:12]=1.C1(C)C(N=C=S)=CC=CC=1.C1(N=C=NC2CCCCC2)CCCCC1.C([OH:62])C>>[C:1]1([CH3:34])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18]([OH:19])=[O:62])[CH:14]=[CH:13][C:11]=2[N:12]=1

Participants

5

Reactant 4

HCID 702Ethanol2×HCID 10868DicyclohexylcarbodiimideHCID 691952-Methylphenyl isothiocyanateHCID 23508312HCID 23508312, compound

Product 1

HCID 235083152-(2-(O-tolylamino)benzo[d]oxazol-6-yl)acetic acid

Procedure

A mixture of ethyl 4-amino-3-hydroxy-phenylacetate (3.3 g, Reference Example 3) and o-tolylisothiocyanate (2.5 mL) in ethanol (150 mL) was stirred at room temperature for about 2 hours. After standing at room temperature overnight the mixture was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3, v/v) to give a yellow foam. A solution of this material in ethanol (150 mL) was treated with dicyclohexylcarbodiimide (3.0 g) and the mixture was heated at reflux temperature for 2 hours. The mixture was evaporated and the residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane to remove dicyclohexylurea. The resulting light yellow oil was dissolved in ethanol (100 mL) and the solution was treated with sodium hydroxide solution (15 mL, 1M) then heated at reflux temperature for 2 hours. The reaction mixture was evaporated and the residue was dissolved in water. The solution was washed with ethyl acetate and the aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid. The resulting white precipitate was collected by filtration, then washed thoroughly with water, and then dried to give the title compound (1.8 g) as a white solid.

Workup

  1. waitAfter standing at room temperature overnight
  2. customthe mixture was evaporated
  3. additionthe residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3
  4. customv/v) to give a yellow foam
  5. temperaturethe mixture was heated
  6. temperatureat reflux temperature for 2 hours
  7. customThe mixture was evaporated
  8. additionthe residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane
  9. customto remove dicyclohexylurea
  10. dissolutionThe resulting light yellow oil was dissolved in ethanol (100 mL)
  11. additionthe solution was treated with sodium hydroxide solution (15 mL, 1M)
  12. temperaturethen heated
  13. temperatureat reflux temperature for 2 hours
  14. customThe reaction mixture was evaporated
  15. dissolutionthe residue was dissolved in water
  16. washThe solution was washed with ethyl acetate
  17. additionthe aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid
  18. filtrationThe resulting white precipitate was collected by filtration
  19. washwashed thoroughly with water
  20. customdried

Sources & evidence

ORD record
ord-0367b6caef7b4403a3f6f95183314bbd
Source dataset
uspto-grants-2004_07
Patent number
US06762199B2

Reaction notes

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