反応 #657286

反応方程式

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

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   workup.STIRRINGfurther stirred at 0° C. for 30 minutes and at room temperature for one hour
2. 2
   その他The reaction mixture was quenched over cold saturated aqueous ammonium chloride
3. 3
   抽出extracted with tert-butyl methyl ether (3×)
4. 4
   洗浄the combined organic phases washed with brine
5. 5
   乾燥dried over sodium sulfate
6. 6
   濃縮concentrated
7. 7
   workup.STIRRINGstirred at room temperature for 10 minutes
8. 8
   ろ過filtered
9. 9
   その他dried

実験手順

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.

出典