Ammonium Chloride → 1,3-Dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline

HRID 618693Notes

Reaction equation

HRID 618693 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:11]=[C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[N:13]1[CH:22]1[CH2:27][CH2:26][C:25](=[O:28])[N:24]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:23]1=[O:36].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:47])(=O)=O)=CC=1.[Cl-].[NH4+]>O1CCCC1.O.C(OCC)(=O)C>[O:21]=[C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12](=[O:11])[N:13]1[C:22]1([F:47])[CH2:27][CH2:26][C:25](=[O:28])[N:24]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[C:23]1=[O:36]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 15408802Tert-butyl 3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidine-1-carboxylate

Product 1

HCID 154280601,3-Dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a similar fashion, lithium bis(trimethylsilyl)amide (24 mL, 24 mmol, 1.0 M) is added to a stirred solution of 1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxopiperidin-3-yl)isoindoline(7.16 g, 20 mmol) in tetrahydrofuran (250 mL) at -40° C. After 1 hour, N-fluorobenzenesulfonimide (7.6 g, 24 mmol) is added to the mixture. The mixture is allowed to reach room temperature and kept overnight. The solution is stirred with ethyl acetate (200 mL), aqueous ammonium chloride (100 ml, sat), and water (100 mL). The aqueous layer is separated and extracted with ethyl acetate (200 mL). The combined organic layers are washed with water (100 mL), brine (100 mL), and dried over sodium sulfate. The solvent is removed in vacuo. The residue is purified by chromatography (silica gel) to give the intermediate 1,3-dioxo-2-(1-tert-butoxycarbonyl-2,6-dioxo-3-fluoropiperidin-3-yl)isoindoline.

Workup

  1. customto reach room temperature
  2. waitkept overnight
  3. customThe aqueous layer is separated
  4. extractionextracted with ethyl acetate (200 mL)
  5. washThe combined organic layers are washed with water (100 mL), brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe solvent is removed in vacuo
  8. customThe residue is purified by chromatography (silica gel)

Sources & evidence

ORD record
ord-409a5f40fcc84c95b2080e2545cda4e3
Source dataset
uspto-grants-1999_09
Patent number
US05955476

Reaction notes

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