Chlorotrimethylsilane → 2,4,6-Trichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylphenylsulfonamide hydrochloride

N,N′-Carbonyldiimidazole (68 mg, 0.420 mmol) was added to a solution of 2-(2-(2,4,6-trichloro-N-methylphenylsulfonamido)ethoxy)acetic acid (acid unit S9) (150 mg, 0.400 mmol) in methylene chloride (4.5 ml) and the mixture was stirred for 1 h at room temperature. A solution of 4-(pyridin-3-yl)piperidin-4-ol (A2) (71 mg, 0.400 mmol) in methylene chloride (2 ml) was subsequently added and the reaction mixture was stirred for 15 h at room temperature. Thereafter, saturated sodium bicarbonate solution (10 ml) was added to the reaction mixture and the aqueous phase was subsequently extracted with methylene chloride (20 ml). The combined organic phases were extracted with saturated sodium chloride solution (10 ml), dried with sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography with diethyl ether/methylene chloride/methanol/ammonia solution (25% aq.) (50:50:5:1). 2,4,6-Trichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylphenylsulfonamide (200 mg. 0.374 mmol) was dissolved in diethyl ether/methyl ethyl ketone (25:2, 27 ml), and chlorotrimethylsilane (88 μl, 0.692 mmol) was slowly added. The mixture was subsequently stirred for 30 min at 0° C. The precipitate formed was filtered off, washed with diethyl ether/hexane and dried.

1. stirringthe reaction mixture was stirred for 15 h at room temperature
2. extractionthe aqueous phase was subsequently extracted with methylene chloride (20 ml)
3. extractionThe combined organic phases were extracted with saturated sodium chloride solution (10 ml)
4. dry with materialdried with sodium sulfate
5. concentrationconcentrated in vacuo
6. customThe crude product was purified by flash chromatography with diethyl ether/methylene chloride/methanol/ammonia solution (25% aq.) (50:50:5:1)
7. stirringThe mixture was subsequently stirred for 30 min at 0° C
8. customThe precipitate formed
9. filtrationwas filtered off
10. washwashed with diethyl ether/hexane
11. customdried

ORDレコード

ord-cb8d8e3c491e4a6aa95cde90bcd0be27

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08580965B2