Triethylamine → HCID 72477080, compound

HRID 1728114Notes

Reaction equation

HRID 1728114 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:32][CH2:33][CH2:34][OH:35])=[C:6]([CH:8]2[C:13]3([C:21]4[C:16](=[CH:17][C:18]([Cl:22])=[CH:19][CH:20]=4)[NH:15][C:14]3=[O:23])[CH:12]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[CH2:11][C:10](=[O:31])[NH:9]2)[CH:7]=1.[F-].[K+].[CH3:38][CH2:39]N(CC)CC>CN(C=O)C.CO>[Cl:22][C:18]1[CH:17]=[C:16]2[NH:15][C:14](=[O:23])[C:13]3([CH:12]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=4)[CH2:11][C:10](=[O:31])[NH:9][CH:8]3[C:6]3[CH:7]=[C:2]([C:38]#[CH:39])[CH:3]=[CH:4][C:5]=3[O:32][CH2:33][CH2:34][OH:35])[C:21]2=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 522689Potassium FluorideHCID 76568091HCID 76568091, compound

Product 1

HCID 72477080HCID 72477080, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of racemic (2′R,3R,4′S)-2′-[5-bromo-2-(2-hydroxy-ethoxy)-phenyl]-6-chloro-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (60 mg, 0.11 mmol) prepared in example 181b in DMF (2 mL), Et3N (0.3 mL), PdCl2(Ph3P)2 (Aldrich, 15 mg) were added and the mixture was purged with nitrogen and sealed. The vessel was heated on a microwave reactor for 25 min. and the mixture was poured into water. The mixture was extracted with EtOAc. The extracts were combined and dried with sodium sulfate and dried to give a brown oil, which was purified by chromatography on an ISCO machine (30-100% EtOAc/Hexanes) to give a foam. 45 mg. The foam was then dissolved in methanol (4 mL) and KF (Aldrich, 53 mg) was added. The mixture was stirred at room temperature overnight. The solvent was removed and the residue was partioned between EtOAc/water. The organic layer was dried and concentrated and the residue was purified by chromatography on ISCO machine (30-100% EtOAc/Hexane) to give an off-white solid. 25 mg.

Workup

  1. customthe mixture was purged with nitrogen
  2. customsealed
  3. temperatureThe vessel was heated on a microwave reactor for 25 min.
  4. additionthe mixture was poured into water
  5. extractionThe mixture was extracted with EtOAc
  6. dry with materialdried with sodium sulfate
  7. customdried
  8. customto give a brown oil, which
  9. customwas purified by chromatography on an ISCO machine (30-100% EtOAc/Hexanes)
  10. customto give a foam
  11. customThe solvent was removed
  12. customThe organic layer was dried
  13. concentrationconcentrated
  14. customthe residue was purified by chromatography on ISCO machine (30-100% EtOAc/Hexane)
  15. customto give an off-white solid

Sources & evidence

ORD record
ord-79775a3afbf7479d820b57995869d997
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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