Chlorotrimethylsilane → 2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)ethanone dihydrochloride

N,N′-Carbonyldiimidazole (272 mg, 1.696 mmol) was added to a solution of 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid (600 mg, 1.615 mmol) in dichloromethane (15 ml), and the mixture was stirred for 1 h at room temperature. A solution of 1-(1-methylpiperidin-4-yl)piperazine (293 mg, 1.615 mmol) in dichloromethane (5 ml) was then added, and the reaction mixture was stirred for 15 h at room temperature. Saturated sodium hydrogen carbonate solution (20 ml) was then added to the reaction mixture, and then the aqueous phase was extracted with dichloromethane (2×20 ml). The combined organic phases were extracted with saturated sodium chloride solution (20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography using dichloromethane/methanol (5:1). 2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)-1-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)ethanone (590 mg, 1.105 mmol) was dissolved in methyl ethyl ketone/ethanol (1:1) (20 ml) [plus a few drops of acetone], and chlorotrimethylsilane (168 μl, 1.326 mmol) was added slowly. Diethyl ether (20 ml) was then added, and the mixture was stirred for 1 h at 0° C. The resulting precipitate was filtered off, dried with the exclusion of air and washed with diethyl ether.

1. stirringthe reaction mixture was stirred for 15 h at room temperature
2. extractionthe aqueous phase was extracted with dichloromethane (2×20 ml)
3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (20 ml)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by flash chromatography
7. additionwas added slowly
8. stirringthe mixture was stirred for 1 h at 0° C
9. filtrationThe resulting precipitate was filtered off
10. customdried with the exclusion of air
11. washwashed with diethyl ether

ORD-Eintrag

ord-5d2629f9f2c7402897e5880385145893

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08435978B2