5-Fluoro-o-tolyl Isothiocyanate → Ethyl (2-(5-fluoro-2-methylphenylamino)-4-fluoro-6-benzoxazolyl)acetate

HRID 1372655Notes

Reaction equation

HRID 1372655 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][C:3]=1[F:15].[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([N:23]=[C:24]=S)[CH:22]=1>CO>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:26])=[C:21]([NH:23][C:24]2[O:8][C:7]3[CH:6]=[C:5]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:4]=[C:3]([F:15])[C:2]=3[N:1]=2)[CH:22]=1

Participants

4

Reactant 2

HCID 5194435-Fluoro-o-tolyl IsothiocyanateHCID 17858886Ethyl 4-amino-3-fluoro-5-hydroxyphenylacetate

Product 1

HCID 58778879Ethyl (2-(5-fluoro-2-methylphenylamino)-4-fluoro-6-benzoxazolyl)acetateYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under stirring at room temperature, ethyl 4-amino-3-fluoro-5-hydroxyphenylacetate (233 mg, 1.10 mmol) was added to a solution of 5-fluoro-2-methylphenyl isothiocyanate (184 mg, 1.10 mmol) in methanol (20 ml). The resulting mixture was stirred at 70° C. for 1 hour. To the reaction mixture was added mercuric oxide (yellow) (262 mg, 1.21 mmol), followed by stirring for further 30 minutes. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was washed with methanol and then, distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/methanol (10/1) eluate fractions, ethyl (2-(5-fluoro-2-methylphenylamino)-4-fluoro-6-benzoxazolyl)acetate (216 mg, 57%) was obtained as a pale yellow solid.

Workup

  1. stirringThe resulting mixture was stirred at 70° C. for 1 hour
  2. stirringby stirring for further 30 minutes
  3. temperatureAfter cooling to room temperature
  4. filtrationthe reaction mixture was filtered through Celite
  5. washThe filtrate was washed with methanol
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent
  8. customThe residue was purified by chromatography on a silica gel column, whereby from chloroform/methanol (10/1) eluate fractions

Sources & evidence

ORD record
ord-9ad03124258f4f03922a8e0876e0d28d
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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