Ethyl formate → 2,6-Dichloro-4-(pyrrolidine-1-carbonyl)-pyridine-3-carbaldehyde

HRID 251635

反応式

HRID 251635 の反応式
[N:1]1([CH:6]=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([Cl:18])[N:17]=1)C(O)=O.[Li+].CC([N-]C(C)C)C.[CH:27](OCC)=[O:28]>C1COCC1>[Cl:18][C:16]1[C:15]([CH:27]=[O:28])=[C:11]([C:6]([N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:7])[CH:10]=[C:9]([Cl:8])[N:17]=1

参加物

6

反応物 4

HCID 8025Ethyl formateHCID 773721-PyrrolidinecarboxaldehydeHCID 948302,6-Dichloroisonicotinic acidHCID 2724682Lithium diisopropylamide

生成物 1

HCID 865939852,6-Dichloro-4-(pyrrolidine-1-carbonyl)-pyridine-3-carbaldehyde

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

To a solution of 2,6-dichloro-pyridin-4-yl)-pyrrolidin-1-yl-methanone (2.0 g, 8.2 mmol, prepared from commercially available 2,6-dichloro-isonicotinic acid) in THF (50 mL) is added slowly LDA (4 mL, 2M in heptane/THF/ethylbenzene), maintaining an internal temperature below −65° C. The solution is stirred at −78° C. for 1 hour, then treated dropwise ethyl formate (640 mg, 8.6 mmol), again maintaining an internal temperature below −65° C. The resulting mixture is gradually warmed to room temperature and stirred overnight. The mixture is quenched with saturated NH4Cl, extracted with ether and the combined extracts are washed with brine, dried over sodium sulfate and concentrated to give crude 2,6-dichloro-4-(pyrrolidine-1-carbonyl)-pyridine-3-carbaldehyde, which is used directly for the next step.

後処理

  1. temperaturemaintaining an internal temperature below −65° C
  2. temperatureagain maintaining an internal temperature below −65° C
  3. temperatureThe resulting mixture is gradually warmed to room temperature
  4. stirringstirred overnight
  5. customThe mixture is quenched with saturated NH4Cl
  6. extractionextracted with ether
  7. washthe combined extracts are washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-ab08aba5d4564124a395abc09f3f602e
出典データセット
uspto-grants-2011_01
特許番号
US07863454B2

関連ノート

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