Methyl iodide → HCID 71060602, compound

HRID 1036723Notes

Reaction equation

HRID 1036723 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][CH2:22][C:10]2([C:14](=[O:15])[NH:13][CH2:12][CH:11]2[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[CH3:26][Si]([N-][Si](C)(C)C)(C)C.IC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][CH2:22][C:10]2([C:14](=[O:15])[N:13]([CH3:26])[CH2:12][CH:11]2[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 2733832Lithium Hexamethyldisilazide2×HCID 710603511-Oxo-4-pyridin-3-yl-2,7-diaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester

Product 1

HCID 71060602HCID 71060602, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent5×

Conditions

Temperature
-60 °C

Procedure

To a cooled (−60° C.) solution of 1-oxo-4-pyridin-3-yl-2,7-diaza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester (diastereomer 1) (343 mg, 1.03 mmol) in THF (7 ml) was added dropwise 1M LHMDS in THF (1.34 ml, 1.34 mmol). After stirring for 1 h at −60° C., iodomethane (0.084 ml, 1.34 mmol) in THF (1 ml) was added. The cooling bath was removed and the reaction mixture was allowed to warm to RT and stirred for 3 h. A further portion of 1M LHMDS in THF (0.75 ml, 0.75 mmol) was added to the cooled (−60° C.) reaction mixture. After 30 minutes, iodomethane (0.042 ml, 0.67 mmol) in THF (0.5 ml) was added, the cooling bath was removed and the reaction mixture was allowed to warm to RT and stirred overnight. The reaction was quenched with NH4Cl saturated solution (5 ml) and extracted with EtOAc (2×25 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 0-5% MeOH in DCM afforded the title compound as a yellow oil.

Workup

  1. customThe cooling bath was removed
  2. temperatureto warm to RT
  3. stirringstirred for 3 h
  4. temperaturecooled
  5. custom(−60° C.) reaction mixture
  6. waitAfter 30 minutes
  7. customthe cooling bath was removed
  8. temperatureto warm to RT
  9. stirringstirred overnight
  10. customThe reaction was quenched with NH4Cl saturated solution (5 ml)
  11. extractionextracted with EtOAc (2×25 ml)
  12. dry with materialThe combined organic extracts were dried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customPurification of the crude product by chromatography on silica eluting with 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-067acf51965f4cf7a0d7e1c7e6bf92f2
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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