4-Amino-3-fluorophenol → HCID 67253219, compound

HRID 409710Notes

Reaction equation

HRID 409710 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10]([OH:15])[CH:11]=[CH:12][C:13]=1[NH2:14].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:18]=1>C(OCC)(=O)C>[NH2:14][C:13]1[CH:12]=[CH:11][C:10]([O:15][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:18]=2)=[CH:9][C:8]=1[F:7]

Participants

5

Reactant 3

HCID 27359194-Amino-3-fluorophenolHCID 11806045tert-Butyl 4-chloropicolinateHCID 23665647Potassium tert-butoxide

Product 1

HCID 67253219HCID 67253219, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Potassium tert-butoxide (5 g, 23.47 mmol, 1.4 eq) was dissolved in N,N-dimethylacetylamide (DMA, 12 mL). A solution of 3-fluoro-4-aminophenol (4.2 g, 32.86 mmol, 1.4 eq) in DMA (15 mL) was slowly added dropwise at 0° C. After the addition, the mixture was stirred at room temperature for 30 min. The mixture was heated to 100° C. and a solution of tert-butyl 4-chloropicolinate in DMA (18 mL) was slowly added dropwise, and then the mixture was stirred for 1 h. After being cooled to room temperature, ethyl acetate (500 mL) was added, and the resulted mixture was filtered to remove the undissolved material. The filtrate was washed with saturated brine (200 mL×3), dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give a brown solid. The crude was purified by column chromatography (petroleum ether: ethyl acetate=3:1) to give the title compound (1.38 g, purity 98%, yield 20%) as a light brown solid.

Workup

  1. additionAfter the addition
  2. temperatureThe mixture was heated to 100° C.
  3. stirringthe mixture was stirred for 1 h
  4. temperatureAfter being cooled to room temperature
  5. filtrationthe resulted mixture was filtered
  6. customto remove the undissolved material
  7. washThe filtrate was washed with saturated brine (200 mL×3)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was removed under reduced pressure
  10. customto give a brown solid
  11. customThe crude was purified by column chromatography (petroleum ether: ethyl acetate=3:1)

Sources & evidence

ORD record
ord-993a73c0e6f046bd853091fd2b93e9d4
Source dataset
uspto-grants-2014_06
Patent number
US08759531B2

Reaction notes

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