Methyl iodide → HCID 58537907, compound

HRID 1473764Notes

Reaction equation

HRID 1473764 reaction equation
[OH:1][C:2]1[C:6]2([CH2:11][CH2:10][N:9]([O:12][CH3:13])[CH2:8][CH2:7]2)[NH:5][C:4](=[O:14])[C:3]=1[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=1[CH3:23].[CH3:24][Si]([N-][Si](C)(C)C)(C)C.[Li+].CI>O1CCCC1>[OH:1][C:2]1[C:6]2([CH2:11][CH2:10][N:9]([O:12][CH3:13])[CH2:8][CH2:7]2)[N:5]([CH3:24])[C:4](=[O:14])[C:3]=1[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=1[CH3:23]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 59614602HCID 59614602, compound

Product 1

HCID 58537907HCID 58537907, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-hydroxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one [starting material (SM) prepared according to WO09/049,851] (500 mg, 1.58 mmol) in tetrahydrofuran (20 ml) at 0° C. was added a 1.0 M lithium bis(trimethylsilyl)amide solution in hexanes (3.32 ml, 3.32 mmol) dropwise over 15 minutes. The mixture was stirred one hour at 0° C., treated with methyl iodide (0.099 ml, 225 mg, 1.59 mmol) dropwise over 10 minutes, and further stirred at 0° C. for 30 minutes and at room temperature for one hour. The reaction mixture was quenched over cold saturated aqueous ammonium chloride and extracted with tert-butyl methyl ether (3×), the combined organic phases washed with brine, dried over sodium sulfate and concentrated. The residue (210 mg) was suspended in hexane, stirred at room temperature for 10 minutes, filtered and dried. Yield: 171 mg of a clean mixture of starting material (SM) and 4-hydroxy-8-methoxy-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (title compound P2.2) as a beige solid.

Workup

  1. stirringfurther stirred at 0° C. for 30 minutes and at room temperature for one hour
  2. customThe reaction mixture was quenched over cold saturated aqueous ammonium chloride
  3. extractionextracted with tert-butyl methyl ether (3×)
  4. washthe combined organic phases washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. stirringstirred at room temperature for 10 minutes
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-11fcd34ead2041e2ac95cb73ae6b4624
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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