5-Chloro-2-methylphenyl isothiocyanate → Methyl (2-(5-chloro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate

HRID 1372642Notes

Reaction equation

HRID 1372642 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:17]=[CH:18][C:19]([CH3:25])=[C:20]([N:22]=[C:23]=S)[CH:21]=1>CO>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([CH3:25])=[C:20]([NH:22][C:23]2[O:14][C:3]3[C:4]([F:13])=[C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:7][C:2]=3[N:1]=2)[CH:21]=1

Participants

4

Reactant 2

HCID 295195-Chloro-2-methylphenyl isothiocyanateHCID 17859032Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate

Product 1

HCID 58778453Methyl (2-(5-chloro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetateYield 104.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In methanol (30 ml) was dissolved methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate (1.0 g, 5.02 mmol). To the resulting solution was added 5-chloro-2-methylphenyl isothiocyanate (0.674 ml, 4.58 mmol). After the mixture was stirred at room temperature for 5 days, mercuric oxide (yellow) (1.14 g, 4.36 mmol) was added thereto. The resulting mixture was stirred at 70° C. for 6 hours. After cooling to room temperature, 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, v/v) eluate fractions, methyl (2-(5-chloro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate (1.67 g, 100%) was obtained as a brown solid.

Workup

  1. stirringThe resulting mixture was stirred at 70° C. for 6 hours
  2. temperatureAfter cooling to room temperature
  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

Sources & evidence

ORD record
ord-872731dd92f545cd9cb6dcde9122e441
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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