1-Hydroxybenzotriazole → 2-[[(2S)-1-[(4-Methoxy-2,6-dimethyl-phenyl)sulfonyl]-piperidin-2-yl]-methoxy]-1-[4-(2-pyrrolidin-1-yl-ethoxy)-4-[3-(trifluoromethyl)phenyl]-piperidin-1-yl]-ethanone

Diisopropylethylamine (4 eq.), EDCl HCl (1.2 eq.) and HOBt (1 eq.) were added to a mixture of (S)-2-((1-(4-methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acid [acid D] (0.65 mmol) in methylene chloride (10 ml). A mixture of 4-(2-(pyrrolidin-1-yl)ethoxy)-4-(3-(trifluoromethyl)phenyl)piperidine [amine H] and DIPEA (2 eq.) in methylene chloride (3 ml) was added dropwise, while cooling with ice, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with methylene chloride, washed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and with sat. sodium chloride solution, dried over sodium sulfate and concentrated. The crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride) to obtain the desired product. Yield: 78%. MS, Rt=3.9 min, m/z=696.4 [MH]+

1. additionwas added dropwise
2. temperaturewhile cooling with ice
3. washwashed with saturated ammonium chloride solution, saturated sodium chloride solution, saturated sodium bicarbonate solution and with sat. sodium chloride solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. customThe crude product was purified by means of column chromatography (silica gel, methanol/methylene chloride)

ORDレコード

ord-90e61eb30af2456bacc174a8bbc43791

出典データセット

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08318769B2