4-Fluoro-2-methylphenyl isothiocyanate → Methyl (2-(4-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate

HRID 1372646Notes

Reaction equation

HRID 1372646 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].[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]=[C:23]=S)=[C:18]([CH3:25])[CH:17]=1>CO>[F:15][C:16]1[CH:21]=[CH:20][C:19]([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)=[C:18]([CH3:25])[CH:17]=1

Participants

4

Reactant 2

HCID 27373994-Fluoro-2-methylphenyl isothiocyanateHCID 17859032Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate

Product 1

HCID 58778975Methyl (2-(4-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetateYield 91%

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 4-fluoro-2-methylphenyl isothiocyanate (0.74 ml, 5.23 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 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) eluate fractions, methyl (2-(4-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate (1.32 g, 91%) was obtained as a colorless solid.

Workup

  1. stirringThe 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) eluate fractions

Sources & evidence

ORD record
ord-741b8b833de44a6c9572b692b6b7b7c3
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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