Réaction #657286

Équation de réaction

methyl iodide

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

lithium bis(trimethylsilyl)amide

→

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

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGfurther stirred at 0° C. for 30 minutes and at room temperature for one hour
2. 2
   AutreThe reaction mixture was quenched over cold saturated aqueous ammonium chloride
3. 3
   Extractionextracted with tert-butyl methyl ether (3×)
4. 4
   Lavagethe combined organic phases washed with brine
5. 5
   Séchagedried over sodium sulfate
6. 6
   Concentrationconcentrated
7. 7
   workup.STIRRINGstirred at room temperature for 10 minutes
8. 8
   Filtrationfiltered
9. 9
   Autredried

Mode opératoire

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 WO09/049851] (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. 1H-NMR and LC-MS analysis of the crude material indicated a ˜1:2.5 ratio of this mixture SM/compound P2.2.

Source