Triethylamine → Ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate

HRID 1047138ノート

反応式

HRID 1047138 の反応式
[Br:1][C:2]1[CH:3]=[N:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.S(Cl)(Cl)=O.[CH3:16][N:17]([CH3:25])[CH:18]=[CH:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(N(CC)CC)C>C1(C)C=CC=CC=1.C1COCC1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([C:19](=[CH:18][N:17]([CH3:25])[CH3:16])[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:9]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 121015Ethyl 3-(N,N-dimethylamino)acrylateHCID 247213715-Bromo-2-fluoropyridine-3-carboxylic acid

生成物 1

HCID 68749333Ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate収率 77.3%

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
110 °C

実験手順

To a solution of 5-bromo-2-fluoronicotinic acid (3 g, 13.64 mmol) in toluene (30 mL) was added thionyl chloride (5 mL, 68.18 mmol, 5 equiv.) followed by DMF (0.5 mL). This was stirred at 110° C. for 2 h then concentrated in vacuo. The residue was resuspended in THF (15 mL) and added dropwise to a solution of ethyl 3-(dimethylamino)acrylate (2 mL, 13.64 mmol) and triethylamine (2.85 mL, 20.45 mmol) in THF (15 mL). The reaction was stirred at 70° C. for 18 h, cooled down to room temperature, and quenched with water. The reaction was partitioned between water (70 mL) and ethyl acetate (70 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×70 mL). The combined organic layers were washed with 1 N HCl (100 mL) and brine (100 mL), dried over sodium sulftate, and concentrated. The concentrate was purified via silica gel chromotography to provide ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate as an orange solid (3.64 g, 77%).

後処理

  1. concentrationthen concentrated in vacuo
  2. stirringThe reaction was stirred at 70° C. for 18 h
  3. temperaturecooled down to room temperature
  4. customquenched with water
  5. customThe reaction was partitioned between water (70 mL) and ethyl acetate (70 mL)
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (2×70 mL)
  8. washThe combined organic layers were washed with 1 N HCl (100 mL) and brine (100 mL)
  9. dry with materialdried over sodium sulftate
  10. concentrationconcentrated
  11. customThe concentrate was purified via silica gel chromotography

出典と根拠

ORDレコード
ord-ae425c3860c94e1ba861e1bcc7741587
出典データセット
uspto-grants-2013_10
特許番号
US08569484B2

反応ノート

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