Methyl iodide → 3-Methyl-4-oxo-1-phenyl-1,3,7-triaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester

HRID 1036718Notes

Reaction equation

HRID 1036718 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][CH2:22][C:10]2([N:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:13][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([N:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:13][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 71060241HCID 71060241, compound

Product 1

HCID 710601793-Methyl-4-oxo-1-phenyl-1,3,7-triaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-oxo-1-phenyl-1,3,7-triaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester (130 mg, 0.45 mmol) in dry THF (3 ml) under nitrogen was cooled to −78° C. and treated with 1M LHMDS in THF (0.55 ml, 0.55 mol). The reaction 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 was left to warm to RT overnight. The reaction mixture was diluted with EtOAc (10 ml) and washed with brine (20 ml). The aqueous phase was extracted with EtOAc (10 ml). 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 was left
  3. temperatureto warm to RT overnight
  4. washwashed with brine (20 ml)
  5. extractionThe aqueous phase was extracted with 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-d45819921512497db019c517121f3c47
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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