2-Methylphenyl isothiocyanate → 2-(4-Methoxy-2-o-tolylaminobenzoxazol-6-yl)acetic acid

HRID 1357861Notes

Reaction equation

HRID 1357861 reaction equation
[NH2:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([CH2:10][C:11]([O:13]C)=[O:12])=[CH:4][C:3]=1[OH:15].[C:16]1([CH3:25])[C:17]([N:22]=[C:23]=S)=[CH:18][CH:19]=[CH:20][CH:21]=1>C(O)C>[CH3:9][O:8][C:7]1[C:2]2[N:1]=[C:23]([NH:22][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH3:25])[O:15][C:3]=2[CH:4]=[C:5]([CH2:10][C:11]([OH:13])=[O:12])[CH:6]=1

Participants

4

Reactant 2

HCID 691952-Methylphenyl isothiocyanateHCID 18188079Methyl 4-amino-3-hydroxy-5-methoxy-phenylacetate

Product 1

HCID 181881002-(4-Methoxy-2-o-tolylaminobenzoxazol-6-yl)acetic acidYield 96.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of methyl 4-amino-3-hydroxy-5-methoxy-phenylacetate [0.295 g, Reference Example 10(a)] and o-tolylisothiocyanate (2.14 g) in ethanol (25 mL) was left at room temperature for 3 days. The mixture was evaporated and a solution of the residue in ethanol (20 mL) was treated with dicyclohexylcarbodiimide (0.308 g). The mixture was heated at reflux temperature for 2.5 hours and then evaporated. The resulting brown oil was dissolved in methanol (30 mL) and the solution was treated with sodium hydroxide solution (10 mL, 1M) and then heated at 45° C. for one hour. The mixtures was diluted with water and then partially evaporated. The residue was washed twice with diethyl ether and the pH of the aqueous phase was adjusted to 1-2 by addition of dilute hydrochloric acid. The mixture was then extracted with ethyl acetate and the organic phase was washed with water, then with brine, then dried and then evaporated to give the title compound (0.42 g) as a golden solid.

Workup

  1. customThe mixture was evaporated
  2. additiona solution of the residue in ethanol (20 mL) was treated with dicyclohexylcarbodiimide (0.308 g)
  3. temperatureThe mixture was heated
  4. temperatureat reflux temperature for 2.5 hours
  5. customevaporated
  6. dissolutionThe resulting brown oil was dissolved in methanol (30 mL)
  7. additionthe solution was treated with sodium hydroxide solution (10 mL, 1M)
  8. additionThe mixtures was diluted with water
  9. custompartially evaporated
  10. washThe residue was washed twice with diethyl ether
  11. additionthe pH of the aqueous phase was adjusted to 1-2 by addition of dilute hydrochloric acid
  12. extractionThe mixture was then extracted with ethyl acetate
  13. washthe organic phase was washed with water
  14. dry with materialwith brine, then dried
  15. customevaporated

Sources & evidence

ORD record
ord-3766cc6cb01245779d36c1903fabc70b
Source dataset
uspto-grants-2003_07
Patent number
US06593354B2

Reaction notes

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