Thionyl Chloride → methyl 6-(2-(methoxycarbonyl)-1H-pyrrol-1-yl)-5-nitronicotinate

HRID 69748

反応式

HRID 69748 の反応式
[NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH3:9])=[O:7].[H-].[Na+].Cl[C:13]1[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=1.S(Cl)(Cl)=O>CS(C)=O.CO>[CH3:9][O:8][C:6]([C:2]1[N:1]([C:13]2[C:22]([N+:23]([O-:25])=[O:24])=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][N:14]=2)[CH:5]=[CH:4][CH:3]=1)=[O:7]

参加物

7

反応物 4

HCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 136930Methyl pyrrole-2-carboxylateHCID 346961Methyl 6-chloro-5-nitronicotinate

生成物 1

HCID 58324515methyl 6-(2-(methoxycarbonyl)-1H-pyrrol-1-yl)-5-nitronicotinate収率 92%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 887Methanol溶媒

反応条件

温度
10 °C

実験手順

Methyl 1H-pyrrole-2-carboxylate (5.78 g, 46.2 mmol) was dissolved in DMSO and cooled to 10° C. NaH was added in two portions over 5 min. The reaction mixture was stirred at 10° C. for 10 min and methyl 6-chloro-5-nitronicotinate (5 g, 23.09 mmol) in DMSO (10 mL) was added slowly over 3 min. The red reaction mixture was allowed to warm to room temperature and stirred overnight. It was cooled to 0° C. and quenched with water (12 mL) and diluted with brine (50 mL). The mixture was washed with EtOAc (2×25 mL) and the aqueous layer was acidified to pH=2 with 4.5 N HCl. It was extracted with EtOAc (1×100 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to afford a yellow solid, which was dissolved in MeOH (100 mL) and cooled to 0° C. Thionyl chloride (45 mL, 617 mmol) was added slowly over 5 min. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature overnight. It was concentrated in vacuo and the resulting solid was triturated with ethyl acetate (300 mL). The solid was filtered off and the filtrate was concentrated in vacuo. then washed with ethyl ether to afford methyl 6-(2-(methoxycarbonyl)-1H-pyrrol-1-yl)-5-nitronicotinate (5.04 g, 16.51 mmol, 92% yield) as a yellow solid, [M+H] calc'd for C13H11N3O6, 306; found, 306.

後処理

  1. customThe red reaction mixture
  2. temperatureto warm to room temperature
  3. stirringstirred overnight
  4. temperatureIt was cooled to 0° C.
  5. customquenched with water (12 mL)
  6. additiondiluted with brine (50 mL)
  7. washThe mixture was washed with EtOAc (2×25 mL)
  8. extractionIt was extracted with EtOAc (1×100 mL)
  9. dry with materialthe organic layer was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto afford a yellow solid, which
  13. temperaturecooled to 0° C
  14. stirringThe reaction mixture was stirred at 0° C. for 1 h
  15. customat room temperature
  16. customovernight
  17. concentrationIt was concentrated in vacuo
  18. customthe resulting solid was triturated with ethyl acetate (300 mL)
  19. filtrationThe solid was filtered off
  20. concentrationthe filtrate was concentrated in vacuo
  21. washthen washed with ethyl ether

出典と根拠

ORDレコード
ord-810db6ac44384e2195c3b1f49a86f625
出典データセット
uspto-grants-2014_09
特許番号
US08822470B2

関連ノート

読み込み中…