Reaktion #59884

Reaktionsgleichung

sodium hydrogen carbonate

methanesulfonyl chloride

2-mercaptobenzimidazole

triethylamine

(4-(5,9-dioxaspiro[3.5]non-7-yloxy)-3-methylpyridin-2-yl)methanol

triethylamine

2-mercaptobenzimidazole

→

title compound

Ausbeute 73.6%

2-(((4-(5,9-dioxaspiro[3.5]non-7-yloxy)-3-methylpyridin-2-yl)methyl)thio)-1H-benzimidazole

Ausbeute 73.6%

Lösungsmittel

tetrahydrofuran

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   ExtraktionThe reaction mixture was extracted with ethyl acetate twice
2. 2
   Waschenwashed with a saturated saline solution
3. 3
   Trocknendried over anhydrous sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   workup.ADDITIONDichloromethane (30 ml) was added to the residue
7. 7
   workup.DISSOLUTIONwas dissolved
8. 8
   workup.STIRRINGAfter the reaction mixture was stirred at room temperature for 2 hours
9. 9
   workup.ADDITIONNH silica gel was added to the reaction mixture, which
10. 10
    Einengenwas then concentrated
11. 11
    WaschenThe residue was subjected to silica gel column chromatography (elution solvent: heptane/ethyl acetate=1/1, ethyl acetate)

Vorschrift

A tetrahydrofuran (20 ml) solution of the (4-(5,9-dioxaspiro[3.5]non-7-yloxy)-3-methylpyridin-2-yl)methanol (630 mg, 2.37 mmol) obtained in the step (9g) and triethylamine (0.66 ml, 4.74 mmol) was stirred at −10° C. After 10 minutes, methanesulfonyl chloride (275 μl, 3.56 mmol) was added at the same temperature and the resultant mixture was stirred in the same conditions for 30 minutes. To the reaction mixture, a saturated aqueous solution of sodium hydrogen carbonate was poured. The reaction mixture was extracted with ethyl acetate twice and organic layers were combined, washed with a saturated saline solution, dried over anhydrous sodium sulfate, filtered and concentrated. Dichloromethane (30 ml) was added to the residue to make a solution, and thereafter, 2-mercaptobenzimidazole (354 mg, 2.36 mmol) was added at room temperature. Furthermore, triethylamine (0.493 ml, 3.54 mmol) was added, and additionally, methanol was added until 2-mercaptobenzimidazole was dissolved. After the reaction mixture was stirred at room temperature for 2 hours, NH silica gel was added to the reaction mixture, which was then concentrated. The residue was subjected to silica gel column chromatography (elution solvent: heptane/ethyl acetate=1/1, ethyl acetate) to obtain the title compound (690 mg, yield: 73.6%) as a white solid.

Quelle