Trifluoroacetic acid → 5,6-Difluoro-2,3-dihydro-1H-isoindol-1-one

HRID 877232Notes

Reaction equation

HRID 877232 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=O)[NH:6][CH:5]2[OH:13].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[F:11][C:10]1[CH:9]=[C:8]2[C:4](=[CH:3][C:2]=1[F:1])[C:5](=[O:13])[NH:6][CH2:7]2

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 581363585,6-Difluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 213653915,6-Difluoro-2,3-dihydro-1H-isoindol-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

748 mg of 5,6-difluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one (crude product, about 4.04 mmol) were initially charged in 50 ml of dichloromethane, 3.8 ml (48.5 mmol) of trifluoroacetic acid and 1.3 ml (8.08 mmol) of triethylsilane were added and the mixture was stirred overnight at RT. The reaction mixture was then concentrated, and the residue was dissolved in dichloromethane and washed with sodium bicarbonate solution. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 1:1 to 0:1). This gave 72 mg (10.6% of theory) of the target compound.

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washwashed with sodium bicarbonate solution
  4. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 1:1 to 0:1)

Sources & evidence

ORD record
ord-f0faaf2f2896460b90cb995aae3a7162
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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