Thiophosgene → Methyl (2-(3-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate

HRID 1372648Notes

Reaction equation

HRID 1372648 reaction equation
[F:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[C:10](Cl)(Cl)=S.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:17]([F:26])[C:16]=1[OH:27]>C1COCC1>[F:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:5][C:10]2[O:27][C:16]3[C:17]([F:26])=[C:18]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH:19]=[CH:20][C:15]=3[N:14]=2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 10040ThiophosgeneHCID 2855533-Fluoro-2-methylanilineHCID 17859032Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate

Product 1

HCID 44607519Methyl (2-(3-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In THF (20 ml) was dissolved 3-fluoro-2-methylaniline (0.57 ml, 5.0 mmol). To the resulting solution was added thiophosgene (990 mg, 5.0 mmol) under stirring at room temperature. After the reaction mixture was stirred for 4 hours at room temperature, methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate (996 mg, 5.0 mmol) was added thereto. The resulting mixture was stirred further at room temperature for 2 days. Mercuric oxide (yellow) (1.08 g, 5.0 mmol) was added and the mixture was stirred at 70° C. for 4.5 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 n-hexane/ethyl acetate (4/1) eluate fractions, methyl (2-(3-fluoro-2-methylphenylamino)-7-fluoro-6-benzoxazolyl)acetate (1.21 g, 73%) was obtained as a colorless solid.

Workup

  1. stirringAfter the reaction mixture was stirred for 4 hours at room temperature
  2. stirringThe resulting mixture was stirred further at room temperature for 2 days
  3. stirringthe mixture was stirred at 70° C. for 4.5 hours
  4. temperatureAfter cooling to room temperature
  5. filtrationthe reaction mixture was filtered through Celite
  6. washwashed with methanol
  7. distillationThe filtrate was distilled under reduced pressure
  8. customto remove the solvent
  9. customThe residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (4/1) eluate fractions

Sources & evidence

ORD record
ord-23140df8c5754693811589f6f0311bd8
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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