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Ammonium Chloride → 2-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester

HRID 1753906
ノート
印刷プレビュー

反応式

HRID 1753906 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2].[CH:20]1([Mg]Br)[CH2:22][CH2:21]1.[Cl-].[NH4+]>O1CCCC1.CN1CCCC1=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH:20]2[CH2:22][CH2:21]2)=[N:8][C:9]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:11]=1[CH3:12])=[O:5])[CH3:2]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 25517Ammonium ChlorideHCID 866719032-Chloro-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl esterHCID 178418630HCID 178418630、化合物

生成物 1

HCID 708168332-Cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester収率 211.4%

試薬・触媒・溶媒 2

HCID 5483663Ferric acetylacetonate
触媒
HCID 22156051tetrahydrofuran N-methylpyrrolidinone溶媒

反応条件

温度
-20 °C

実験手順

To a solution 2-chloro-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester (7.0 g, 24.6 mmol) in tetrahydrofuran-N-methyl-2-pyrrolidone (2:3) (250 ml) is added iron(III) acetylacetonate (1.74 g, 4.92 mmol) and the mixture is cooled to −20° C. At this temperature, a solution of cyclopropylmagnesium bromide (0.7 M in tetrahydrofuran) (105 ml, 73.8 mmol) is slowly added and the mixture is warmed to 0° C. within 30 min. After completion of the reaction, 10% aqueous ammonium chloride is added and the mixture is extracted with ethyl acetate (2×). The combined organic layers are washed with water and brine, dried over magnesium sulphate and evaporated to dryness. The reaction is repeated once and the combined crude products are purified by flash chromatography (silica gel, 75% ethyl acetate/cyclohexane) to yield 2-cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid ethyl ester (15.1 g).

後処理

  1. temperaturethe mixture is warmed to 0° C. within 30 min
  2. additionis added
  3. extractionthe mixture is extracted with ethyl acetate (2×)
  4. washThe combined organic layers are washed with water and brine
  5. dry with materialdried over magnesium sulphate
  6. customevaporated to dryness
  7. customthe combined crude products are purified by flash chromatography (silica gel, 75% ethyl acetate/cyclohexane)

出典と根拠

ORDレコード
ord-915eb9545be342ed95a6283ba0b07327
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09168259B2

反応ノート

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