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

HRID 1357857Notes

Reaction equation

HRID 1357857 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11]CC)=[O:10])=[CH:4][C:3]=1[OH:14].[C:15]1([CH3:24])[C:16]([N:21]=[C:22]=S)=[CH:17][CH:18]=[CH:19][CH:20]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(O)C>[C:15]1([CH3:24])[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22]1[O:14][C:3]2[CH:4]=[C:5]([CH2:8][C:9]([OH:11])=[O:10])[CH:6]=[CH:7][C:2]=2[N:1]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 691952-Methylphenyl isothiocyanateHCID 23508323Ethyl 2-(4-amino-3-hydroxyphenyl)acetate

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of ethyl 4-amino-3-hydroxy-phenylacetate (3.3 g, Reference Example 5) 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 tert-butyl methyl ether and dichloromethane, 1:19 to 1:9 v/v). 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. additionwith a mixture of pentane and ethyl acetate, 7:3 v/v)
  4. customto give a yellow foam
  5. temperaturethe mixture was heated
  6. temperatureat reflux temperature for 2 hours
  7. customThe mixture was evaporated
  8. additionwith a mixture of tert-butyl methyl ether and dichloromethane, 1:19 to 1:9 v/v)
  9. dissolutionThe resulting light yellow oil was dissolved in ethanol (100 mL)
  10. additionthe solution was treated with sodium hydroxide solution (15 mL, 1M)
  11. temperaturethen heated
  12. temperatureat reflux temperature for 2 hours
  13. customThe reaction mixture was evaporated
  14. dissolutionthe residue was dissolved in water
  15. washThe solution was washed with ethyl acetate
  16. additionthe aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid
  17. filtrationThe resulting white precipitate was collected by filtration
  18. washwashed thoroughly with water
  19. customdried

Sources & evidence

ORD record
ord-6b22d5db5e53439791aaba14dbe32c62
Source dataset
uspto-grants-2003_07
Patent number
US06593354B2

Reaction notes

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