Reaction #657277

Reaction equation

methyl iodide

4-benzyloxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one

lithium bis(trimethylsilyl)amide

→

4-benzyloxy-8-methoxy-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGStirring
2. 2
   workup.WAITwas continued at room temperature overnight
3. 3
   Otherthe reaction mixture was quenched with cold saturated aqueous ammonium chloride
4. 4
   OtherThe layers were separated
5. 5
   Extractionthe aqueous phase extracted twice with ethyl acetate
6. 6
   Washthe combined organic phases washed with brine
7. 7
   Dryingdried over sodium sulfate
8. 8
   Concentrationconcentrated
9. 9
   workup.STIRRINGstirred for 30 minutes
10. 10
    Filtrationfiltered
11. 11
    Otherdried

Procedure

To a solution of 4-benzyloxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (40.0 g, 98.4 mmol) in tetrahydrofuran (500 ml) at 0° C. was added a 1.0 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (108.3 ml, 108.3 mmol) dropwise over one hour. The mixture was stirred at 0° C. for 30 minutes and at room temperature for 30 minutes, then treated with methyl iodide (6.75 ml, 15.4 g, 108.2 mmol) dropwise at 0° C. over 10 minutes. Stirring was continued at room temperature overnight and the reaction mixture was quenched with cold saturated aqueous ammonium chloride. The layers were separated, the aqueous phase extracted twice with ethyl acetate, the combined organic phases washed with brine, dried over sodium sulfate and concentrated. The residue was suspended in diethyl ether, stirred for 30 minutes, filtered and dried. Yield: 28.6 g of 4-benzyloxy-8-methoxy-1-methyl-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P3.5) as a solid, mp 139-141° C.

Source