Hydrochloric Acid → 5'-Methyl-3,4,5,6-tetrahydro[2,3']bipyridinyl dihydrochloride

HRID 1670788ノート

反応式

HRID 1670788 の反応式
C(N(C[N:7]1[CH2:12][CH2:11][CH2:10][C:9](=[C:13](O)[C:14]2[CH:15]=[N:16][CH:17]=[C:18]([CH3:20])[CH:19]=2)C1=O)CC)C.[ClH:23]>CC(C)=O.C(O)(C)C>[ClH:23].[ClH:23].[CH3:20][C:18]1[CH:19]=[C:14]([C:13]2[CH2:9][CH2:10][CH2:11][CH2:12][N:7]=2)[CH:15]=[N:16][CH:17]=1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 670247281-Diethylaminomethyl-3-[hydroxy-(5-methylpyridin-3-yl)methylene]piperidin-2-one

生成物 1

HCID 670246865'-Methyl-3,4,5,6-tetrahydro[2,3']bipyridinyl dihydrochloride収率 85%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 3776Isopropanol溶媒

反応条件

温度
100 °C

実験手順

To a solution of diisopropylamine (4.4 mL, 31.4 mmol) in tetrahydrofuran (20 mL) at −78° C. was added a 2.5 M solution of n-butyllithium in hexanes (12 mL, 30 mmol). The solution was allowed to warm to rt over 30 min and was re-cooled to −78° C. A solution of 1-diethylaminomethyl-piperidin-2-one (3.87 g, 21.0 mmol) in tetrahydrofuran (10 mL) was added to the lithium diisopropylamide via syringe. The reaction mixture was maintained at −78° C. for 1 h and was treated with a solution of 5-methylnicotinic acid methyl ester (2.12 g, 14.0 mmol) in tetrahydrofuran (20 mL) via syringe. The reaction mixture was allowed to warm to rt and was maintained overnight. The reaction mixture was quenched with water (30 mL) and was extracted with ether (2×). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography [1/0 to 1/1 ethyl acetate/(70/30/1 ethyl acetate/methanol/ammonium hydroxide)] to provide 560 mg (13%) of 1-diethylaminomethyl-3-[hydroxy-(5-methylpyridin-3-yl)methylene]piperidin-2-one. To a solution of the piperidin-2-one (550 mg, 1.8 mmol) in acetone (10 mL) was added conc. hydrochloric acid (2 L) and the reaction mixture was heated at 100° C. overnight. The reaction mixture was allowed to cool to rt, diluted with isopropyl alcohol, and allowed to stand at 0° C. The product was isolated by filtration, thus providing 400 mg (85%) of 5′-methyl-3,4,5,6-tetrahydro[2,3′]bipyridinyl dihydrochloride.

後処理

  1. temperatureto cool to rt
  2. customto stand at 0° C
  3. customThe product was isolated by filtration

出典と根拠

ORDレコード
ord-c6e4b12c6f914a5283ce1a7d62735373
出典データセット
uspto-grants-2011_08
特許番号
US07994199B2

反応ノート

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