Toluene → 3-Fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride

HRID 1433943노트

반응식

HRID 1433943 반응식
[ClH:1].[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:6](O)=[O:7].C1(C)C=CC=CC=1>S(Cl)(Cl)=O>[ClH:1].[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:6]([Cl:1])=[O:7]

참가 물질

4

반응물 2

HCID 1140TolueneHCID 666268273-Fluoro-4-(2-piperidin-1-ylethoxy)benzoic acid hydrochloride

생성물 1

HCID 230871263-Fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride수율 165.9%

시약·촉매·용매 1

HCID 24386Thionyl Chloride용매

반응 조건

온도
110 °C

실험 절차

To a solution of 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoic acid hydrochloride (2.5 g) in thionyl chloride (25 ml) was added toluene (25 ml), the solution was stirred for 1.5 hours at 110° C., and then the reaction solution was concentrated in vacuo to provide 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride (2.2 g). To a solution of 5-methoxy-2-(6-methoxynaphthalen-2-yl)phenylamine (280 mg) in pyridine (3 ml) was added 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride (420 mg), and the solution was stirred overnight at room temperature. A saturated aqueous solution of sodium bicarbonate was added thereto, the solution was stirred, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate-methanol system) to provide 3-fluoro-N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(3-piperidin-1-ylethoxy)benzamide (448 mg). To a suspension of lithium aluminum hydride (130 mg) in tetrahydrofuran (3 ml) was added aluminum chloride (455 mg) on an ice bath under a nitrogen atmosphere, the solution was stirred for 30 minutes at room temperature, then 3-fluoro-N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benzamide (446 mg) was added thereto followed by stirring overnight at room temperature. Obtained by sequentially adding tetrahydrofuran and aqueous ammonia, the suspension was filtered through celite pad, and then the filtrate was concentrated in vacuo to provide the title compound (396 mg).

후처리

  1. concentrationthe reaction solution was concentrated in vacuo

출처 및 근거

ORD 기록
ord-b09fe53aa6a540edbe7948d43817992d
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612114B2

반응 노트

불러오는 중…