Hydrochloric Acid → 2-(4-Tert-butyl-phenyl)-4-fluoro-1-hydroxy-1,2-dihydro-pyrrolo[3,4-c]pyridin-3-one

HRID 2251855ノート

反応式

HRID 2251855 の反応式
CC1(C)CCCC(C)(C)N1.[Li]CCCC.[C:16]([C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:35])[C:28]2[CH:33]=[CH:32][CH:31]=[N:30][C:29]=2[F:34])=[CH:22][CH:21]=1)([CH3:19])([CH3:18])[CH3:17].CN([CH:39]=[O:40])C.Cl.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1>[C:16]([C:20]1[CH:21]=[CH:22][C:23]([N:26]2[CH:39]([OH:40])[C:33]3[CH:32]=[CH:31][N:30]=[C:29]([F:34])[C:28]=3[C:27]2=[O:35])=[CH:24][CH:25]=1)([CH3:19])([CH3:17])[CH3:18]

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 130352,2,6,6-TetramethylpiperidineHCID 21959540n-(4-Tert-butylphenyl)-2-fluoronicotinamideHCID 178418339Butyllithium

生成物 1

HCID 690319892-(4-Tert-butyl-phenyl)-4-fluoro-1-hydroxy-1,2-dihydro-pyrrolo[3,4-c]pyridin-3-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To the solution of 2,2,6,6-tetramethylpiperidine (5.0 ml, 30.0 mmol) in 60 mL of anhydrous THF at −78° C. was added n-BuLi (2.5 M solution in hexanes, 16 mL, 40.0 mmol) under N2. The resulting mixture was stirred at −78° C. for 30 min, and a solution of N-(4-tert-butyl-phenyl)-2-fluoro-nicotinamide (2.72 g, 10.0 mmol, Step A) in 20 mL of THF was added dropwise. The mixture was stirred at −78° C. for 2 h, DMF (4.6 mL, 60.0 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min, then gradually warmed to RT. 1N HCl was added to bring pH to 2, then Na2CO3 was added to bring pH to 10. The mixture was extracted with EtOAc, the combined organic portions were dried with MgSO4, filtered, and condensed. The titled compound was obtained as a light-yellowish solid after column chromatography. MS (ES+): 301.2 (M+H)+. Calc'd for C17H17FN2O2-300.33.

後処理

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. stirringThe mixture was stirred at −78° C. for 30 min
  3. temperaturegradually warmed to RT
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialthe combined organic portions were dried with MgSO4
  6. filtrationfiltered
  7. customcondensed

出典と根拠

ORDレコード
ord-da5b426ba8384978b8304edd3f2f06fa
出典データセット
uspto-grants-2008_01
特許番号
US07320992B2

反応ノート

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