Methyl iodide → HCID 71060352, compound

HRID 1036712Notes

Reaction equation

HRID 1036712 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][CH2:22][C:10]2([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:13][NH:12][C:11]2=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[CH3:26][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][CH2:22][C:10]2([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:13][N:12]([CH3:26])[C:11]2=[O:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 71060155HCID 71060155, compound

Product 1

HCID 71060352HCID 71060352, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of racemic mixture of 4-Oxo-1-phenyl-2,3,7-triaza-spiro[4.5]dec-1-ene-7-carboxylic acid tert-butyl ester (150 mg, 0.45 mmol) in THF (3 ml) under nitrogen at −78° C. was added 1M LiHMDS solution in THF (0.55 ml, 0.55 mol). The reaction mixture was allowed to warm to RT for 30 mins before cooling back to −78° C. and adding 2M MeI in THF solution (0.45 ml, 0.9 mmol). The reaction mixture was left to warm to RT overnight. The mixture was diluted with EtOAc (10 ml) and washed with brine (20 ml). The aqueous phase was extracted with a further EtOAc (10 ml). The organics portions were combined, dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-50% EtOAc in iso-hexane afforded the title compound.

Workup

  1. temperaturebefore cooling back to −78° C.
  2. waitThe reaction mixture was left
  3. temperatureto warm to RT overnight
  4. washwashed with brine (20 ml)
  5. extractionThe aqueous phase was extracted with a further EtOAc (10 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude product by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-ff117ccae9934facb7d697b578b4d813
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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