2-Chloro-6-Methylphenyl Isothiocyanate → Methyl (2-(2-chloro-6-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate

HRID 1372640Notes

Reaction equation

HRID 1372640 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[C:4]([F:13])[C:3]=1[OH:14].[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[C:17]=1[N:23]=[C:24]=S>CO>[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH3:22])[C:17]=1[NH:23][C:24]1[O:14][C:3]2[C:4]([F:13])=[C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:7][C:2]=2[N:1]=1

Participants

4

Reactant 2

HCID 37317252-Chloro-6-Methylphenyl IsothiocyanateHCID 17859032Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate

Product 1

HCID 58778824Methyl (2-(2-chloro-6-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetateYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate (1.0 g, 5.02 mmol) was dissolved in methanol (30 ml). To the resulting solution was added 2-chloro-6-methylphenyl isothiocyanate (841 mg, 4.58 mmol) at room temperature. After the resulting mixture was stirred for 5 days, mercuric oxide (yellow) (1.14 g, 4.36 mmol) was added thereto. The mixture was stirred at 70° C. for 23 hours. After cooling, the reaction mixture was filtered through Celite and washed with methanol. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (30/1) eluate fractions, methyl (2-(2-chloro-6-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate (1.45 g, 95%) was obtained as a red amorphous substance.

Workup

  1. stirringThe mixture was stirred at 70° C. for 23 hours
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered through Celite
  4. washwashed with methanol
  5. distillationThe filtrate was distilled under reduced pressure
  6. customto remove the solvent
  7. customThe residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (30/1) eluate fractions

Sources & evidence

ORD record
ord-39222855ccf64d6d8c3f0588acd1d821
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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