Trifluoroacetic acid → 2,3-dihydro-2-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-1H-isoindol-1-one

HRID 1082419Notes

Reaction equation

HRID 1082419 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH:25](O)[C:24]5[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=5)[C:18]4=[O:27])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+]>ClCCl>[F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH2:25][C:24]5[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=5)[C:18]4=[O:27])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 184672142-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl-2,3-dihydro-3-hydroxy-1H-isoindol-1-one

Product 1

HCID 184673572,3-dihydro-2-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-1H-isoindol-1-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2,3-dihydro-3-hydroxy-1H-isoindol-1-one (2.2 g, 5.6 mmol) was added a solution of trifluoroacetic acid (11.0 ml) in dichloromethane (30 ml) at room temperature, under nitrogen. Triethylsilane (1.5 ml) was then added and the reaction mixture was allowed to stir for 18 hours at which time it was poured into a NaHCO3 (sat.). The layers were separated and the aqueous phase was extracted with DCM (3×). The combined organics were washed with brine and dried (Na2SO4). Filtration and concentration gave the crude product as a solid which was recrystallized from EtOAc to give 1.6 g (79%) of the desired product as a white solid, m.p.=166°-168° C.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with DCM (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationFiltration and concentration
  6. customgave the crude product as a solid which
  7. customwas recrystallized from EtOAc

Sources & evidence

ORD record
ord-3db36d58eb9d404bae9f3d9497c3cd69
Source dataset
uspto-grants-1996_12
Patent number
US05589488

Reaction notes

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