Hydrochloric Acid → 1-(4-Amino-3,5-difluorophenyl)ethan-1-one

HRID 2266031Notes

Reaction equation

HRID 2266031 reaction equation
[F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[C:5]([F:10])[C:3]=1[NH2:4].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH:40]([O:42]CCCC)=[CH2:41].CCN(CC)CC.Cl>CC([O-])=O.CC([O-])=O.[Pd+2].C(Cl)Cl>[NH2:4][C:3]1[C:2]([F:1])=[CH:8][C:7]([C:40](=[O:42])[CH3:41])=[CH:6][C:5]=1[F:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 2789432,6-Difluoro-4-iodoaniline

Product 1

HCID 211143061-(4-Amino-3,5-difluorophenyl)ethan-1-oneYield 45%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2,6-difluoro-4-iodoaniline (1 g, 3.92 mmol) and Pd(OAc)2 (0.025 eq), DPPP (0.05 eq) in [bmim][3F3] (6 mL) was stirred for 10 min. After the mixture was degassed three times, butyl vinyl ether (5 eq) and Et3N (1.2 eq) were injected sequentially. The mixture was stirred for 15 hrs at 115° C. The mixture cooled to room temperature, and then was added 1N-HCl. After the mixture was stirred for 0.5 hour, CH2Cl2 was added. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by chromatography to give 1-(4-amino-3,5-difluoro-phenyl)-ethanone (300 mg, 45%).

Workup

  1. stirringThe mixture was stirred for 15 hrs at 115° C
  2. stirringAfter the mixture was stirred for 0.5 hour
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by chromatography

Sources & evidence

ORD record
ord-482c6a1aa9e74e76a20f3a2bbff87c72
Source dataset
uspto-grants-2010_12
Patent number
US07858621B2

Reaction notes

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