Carbon Dioxide → 6-((tert-Butoxycarbonyl)amino)-2,3-difluorobenzoic acid

HRID 1378007Notes

Reaction equation

HRID 1378007 reaction equation
C([Li])(C)(C)C.[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[CH:15]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[C:22](=[O:24])=[O:23].O>O1CCCC1>[C:6]([O:10][C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([F:21])[C:15]=1[C:22]([OH:24])=[O:23])=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 962WaterHCID 2783369Carbamic acid, (3,4-difluorophenyl)-, 1,1-dimethylethyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 229144216-((tert-Butoxycarbonyl)amino)-2,3-difluorobenzoic acidYield 76.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

400 ml (600 mmol) of tert.butyllithium (1.5M in pentane) were added dropwise within 1 hour to a solution, cooled to -70°, of 57.2 g (250 mmol) of N-(tert.butoxycarbonyl)-3,4-difluoroaniline in 500 ml of tetrahydrofuran. Subsequently, 160 g of dry ice were added in small portions to the yellow suspension, the mixture was left to warm to 0° and 400 ml of water were added dropwise. The tetrahydrofuran and the pentane were distilled off and the aqueous phase was washed twice with ether and subsequently adjusted to pH=1 with conc. hydrochloric acid. The acidic aqueous phase was extracted three times with methylene chloride; the organic phase was dried over sodium sulfate, filtered and evaporated. The beige solid obtained was recrystallized from ethylene chloride and there were obtained 52 g (76%) of 2-(tert.-butoxycarbonyl)amino-5,6-difluorobenzoic acid as colourless needles of m.p. 159.5°-160.5°.

Workup

  1. waitthe mixture was left
  2. temperatureto warm to 0°
  3. distillationThe tetrahydrofuran and the pentane were distilled off
  4. washthe aqueous phase was washed twice with ether
  5. extractionThe acidic aqueous phase was extracted three times with methylene chloride
  6. dry with materialthe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe beige solid obtained
  10. customwas recrystallized from ethylene chloride

Sources & evidence

ORD record
ord-0a890e2faafd4cd9907f694f127cf9d0
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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