Реакция #2254194

Уравнение реакции

1,9-nonanediol

sodium hydroxide

sodium hydroxide

dimethyl sulfate

dimethyl sulfate

sodium hydroxide

→

9-methoxy-1-nonanol

Выход 21.9%

Растворители

dimethyl sulfoxide

H2O

H2O

Условия реакции

Обработка

1. 1
   Другоеa 500-mL, one-necked, round-bottom flask equipped with a magnetic stirrer
2. 2
   Температураgenerated heat
3. 3
   Другоеrose to ˜40° C
4. 4
   workup.STIRRINGThe mixture was stirred for one hour
5. 5
   workup.STIRRINGThe reaction mixture was stirred at room temperature overnight
6. 6
   workup.STIRRINGthe resulting mixture was stirred at room temperature for an additional 24 h
7. 7
   workup.ADDITIONwas added to the reaction mixture
8. 8
   workup.STIRRINGThe mixture was stirred at room temperature for 2 h
9. 9
   Экстракцияextracted with dichloromethane (3×100 mL)
10. 10
    ПромывкаThe combined organic layers were washed with H2O (200 mL), brine (150 mL)
11. 11
    Сушкаdried over anhydrous sodium sulfate (20 g)
12. 12
    Фильтрацияfiltered
13. 13
    Концентрированиеconcentrated in vacuo
14. 14
    Другоеto obtain a crude product (14 g)
15. 15
    ДругоеThe crude product was purified by column chromatography
16. 16
    Промывкаto elute the product from the column
17. 17
    workup.ADDITIONAll fractions containing the desired pure product
18. 18
    Концентрированиеconcentrated in vacuo

Методика

a 500-mL, one-necked, round-bottom flask equipped with a magnetic stirrer and stir bar was charged with 1,9-nonanediol (10.00 g, 62.3 mmol) in dimethyl sulfoxide (100 mL) and H2O (100 mL). To this was added slowly a solution of sodium hydroxide (5.0 g, 125.0 mmol) in H2O (10 mL) at room temperature. During addition of sodium hydroxide the reaction mixture generated heat and the temperature rose to ˜40° C. The mixture was stirred for one hour, and then dimethyl sulfate (16.52 g, 131 mmol) was added in four portions while maintaining the temperature of the reaction mixture at ˜40° C. The reaction mixture was stirred at room temperature overnight. Progress of the reaction was monitored by TLC (Note 1). TLC monitoring indicated that the reaction was 25% conversion. At this stage additional dimethyl sulfate (24.78 g, 196.44 mmol) was added and the resulting mixture was stirred at room temperature for an additional 24 h. After completion of the reaction, sodium hydroxide (10% solution in water) was added to the reaction mixture to adjust the pH of the solution to 11-13. The mixture was stirred at room temperature for 2 h and extracted with dichloromethane (3×100 mL). The combined organic layers were washed with H2O (200 mL), brine (150 mL), dried over anhydrous sodium sulfate (20 g), filtered and concentrated in vacuo to obtain a crude product (14 g). The crude product was purified by column chromatography using 250-400 mesh silica gel. A solvent gradient of ethyl acetate in hexanes (10-50%) was used to elute the product from the column. All fractions containing the desired pure product were combined and concentrated in vacuo to give pure 9-methoxy-1-nonanol (lot D-1027-155, 2.38 g, 21.9%). Completion of the reaction was monitored by thin layer chromatography (TLC) using a thin layer silica gel plate; eluent: 60% ethyl acetate in hexanes.

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