Formic Acid → HCID 57495860, compound

HRID 2244372Notes

Reaction equation

HRID 2244372 reaction equation
C(O)=O.[C:4](OC(=O)C)(=O)C.[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[F:19]>C1COCC1>[Cl:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][CH3:4])=[CH:14][C:13]=1[F:19]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 27365114-Chloro-3-fluoroaniline

Product 1

HCID 57495860HCID 57495860, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

Formic acid (1.76 ml) was added to acetic acid anhydride (0.91 ml) at 0° C. The solution was stirred for 10 min at this temperature. The reaction was heated under nitrogen to 55° C. for 2 h. The reaction mixture was cooled to 0° C. 4-Chloro-3-fluoroaniline (1.07 g) dissolved in THF (2 ml) was added and the reaction was stirred over night at RT. The solvent was evaporated in vacuo. The residue was dissolved in THF (4 ml). The solution was cooled to 0° C. and borane tetrahydrofuran complex 1M in THF (16.2 ml) was added slowly. Strong gas evolution was observed. The reaction was heated to reflux for 3 h, then cooled to 0° C. and MeOH (4 ml) was added dropwise. The reaction was stirred for 1 h and 1M aq HCl solution (6 ml) was added. The reaction was stirred over night at RT. The solvent was removed in vacuo and the pH of the aqueous layer was adjusted to 9 with 2N aq NaOH solution. The reaction mixture was extracted twice with diethyl ether and the combined organic layers were dried over sodium sulfate, filtered and the solvent was removed in vacuo to yield (4-chloro-3-fluoro-phenyl)-methyl-amine (1150 mg, 98%) as a light brown oil. 1HNMR (DMSO-d6, 300 MHz): δ 2.65 (d, J=5.1 Hz, 3H), 6.15 (d, J=5.1 Hz, 1H), 6.20 (dd, J=3.0 and J=8.4 Hz, 1H), 6.45 (dd, J=2.4 and 12.3 Hz, 1H), 7.18 (t, J=8.7 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C
  2. additionwas added
  3. stirringthe reaction was stirred over night at RT
  4. customThe solvent was evaporated in vacuo
  5. dissolutionThe residue was dissolved in THF (4 ml)
  6. temperatureThe solution was cooled to 0° C.
  7. additionborane tetrahydrofuran complex 1M in THF (16.2 ml) was added slowly
  8. temperatureThe reaction was heated
  9. temperatureto reflux for 3 h
  10. temperaturecooled to 0° C.
  11. additionMeOH (4 ml) was added dropwise
  12. stirringThe reaction was stirred for 1 h
  13. addition1M aq HCl solution (6 ml) was added
  14. stirringThe reaction was stirred over night at RT
  15. customThe solvent was removed in vacuo
  16. extractionThe reaction mixture was extracted twice with diethyl ether
  17. dry with materialthe combined organic layers were dried over sodium sulfate
  18. filtrationfiltered
  19. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-9a924b25e4814faeae4dcdae04d2980b
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

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