Acetic Acid → 2-Cyclopropylamino-4,5-difluorobenzoic acid

HRID 729387

Reaction equation

HRID 729387 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:12])[C:5](=[CH:9][C:10]=1[F:11])[C:6]([OH:8])=[O:7].C(O)(=O)C.C(O[C:20]1(O[Si](C)(C)C)[CH2:22][CH2:21]1)C.C([BH3-])#N.[Na+]>CO.C(OCC)(=O)C>[CH:20]1([NH:12][C:4]2[CH:3]=[C:2]([F:1])[C:10]([F:11])=[CH:9][C:5]=2[C:6]([OH:8])=[O:7])[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7359652-Amino-4,5-difluorobenzoic acidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 149974732-Cyclopropylamino-4,5-difluorobenzoic acidYield 94.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4,5-difluoroanthranilic acid (1.13 g, 6.53 mmol) in anhydrous methanol (40 mL) is added molecular sieves (3 Å), acetic acid (3.70 mL, 65.3 mmol) and [(1-ethoxycyclopropyl)oxy]trimethylsilane (5.25 mL, 26.11 mmol). After 30 minutes, sodium cyanoborohydride (2.08 g, 32.64 mmol) is added, and the reaction mixture is heated to reflux. After 16 hours, the reaction is cooled to room temperature, filtered, washed with methanol, and the combined filtrate concentrated under vacuum to afford a viscous oil. The resulting oil is dissolved in ethyl acetate and washed with 1.0 M hydrochloric acid, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate is concentrated under vacuum to afford as a beige solid (1.32 g). MS CI: m/z 212 (M+).

Workup

  1. temperaturethe reaction mixture is heated to reflux
  2. waitAfter 16 hours
  3. filtrationfiltered
  4. washwashed with methanol
  5. concentrationthe combined filtrate concentrated under vacuum
  6. customto afford a viscous oil
  7. washwashed with 1.0 M hydrochloric acid, water, and brine
  8. dry with materialThe organic layer is dried over MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated under vacuum

Sources & evidence

ORD record
ord-683fbc7e9aab429c86e45384ee7f4e3a
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Linked notes

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