Iodine → HCID 67003641, compound

HRID 1521989Notes

Reaction equation

HRID 1521989 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][N:23]=[C:22]2[N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[CH:28]=[CH:29][C:21]=12.C([N-]C(C)C)(C)C.[Li+].[I:48]I>O1CCCC1>[Cl:19][C:20]1[C:25]([Cl:26])=[CH:24][N:23]=[C:22]2[N:27]([S:30]([C:33]3[CH:39]=[CH:38][C:36]([CH3:37])=[CH:35][CH:34]=3)(=[O:32])=[O:31])[C:28]([I:48])=[CH:29][C:21]=12

Participants

8

Reactant 6

HCID 807IodineHCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 67003430HCID 67003430, compoundHCID 178418339Butyllithium

Product 1

HCID 67003641HCID 67003641, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

To a solution of diisopropylamine (4.85 mL, 34.1 mmol) in tetrahydrofuran (50 mL) at −10° C. under nitrogen was added dropwise 2.5M n-butyllithium in hexane (13.62 mL, 34.1 mmol) and the mixture was stirred at −10° C. for 30 minutes. A solution of Example 229A (8.3 g, 24.33 mmol) in tetrahydrofuran (220 mL) cooled to −78° C. was treated with the lithium diisopropylamide solution dropwise over 20 minutes and the mixture was stirred for 50 minutes at −78° C. A solution of iodine (8.64 g, 34.1 mmol) in tetrahydrofuran (30 mL) was added and the mixture was stirred for 20 minutes at −78° C. and allowed to warm to room temperature. The reaction was quenched with saturated aqueous sodium thiosulfate and extracted with ethyl acetate (150 mL). The organic layer was washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (AnaLogix IntelliFlash 280) eluting with a gradient of 30-60% ethyl acetate in hexanes. The solid was triturated with 100 mL 15% ethyl acetate/hexane, filtered and dried under vacuum to afford the title compound. MS (ESI+) m/z 466.7 (M+H)+.

Workup

  1. stirringthe mixture was stirred for 50 minutes at −78° C
  2. stirringthe mixture was stirred for 20 minutes at −78° C.
  3. temperatureto warm to room temperature
  4. customThe reaction was quenched with saturated aqueous sodium thiosulfate
  5. extractionextracted with ethyl acetate (150 mL)
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (AnaLogix IntelliFlash 280)
  11. washeluting with a gradient of 30-60% ethyl acetate in hexanes
  12. customThe solid was triturated with 100 mL 15% ethyl acetate/hexane
  13. filtrationfiltered
  14. customdried under vacuum

Sources & evidence

ORD record
ord-d5aaee2084564878ae93f3dd42289c96
Source dataset
uspto-grants-2015_07
Patent number
US09073922B2

Reaction notes

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