Hydrochloric Acid → 2-(4-Tert-butyl-phenyl)-4-fluoro-1-hydroxy-1,2-dihydro-pyrrolo[3,4-c]pyridin-3-one
Reaction equation
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]Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
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.
Workup
- stirringThe mixture was stirred at −78° C. for 2 h
- stirringThe mixture was stirred at −78° C. for 30 min
- temperaturegradually warmed to RT
- extractionThe mixture was extracted with EtOAc
- dry with materialthe combined organic portions were dried with MgSO4
- filtrationfiltered
- customcondensed
Sources & evidence
- ORD record
- ord-da5b426ba8384978b8304edd3f2f06fa
- Source dataset
- uspto-grants-2008_01
- Patent number
- US07320992B2
Reaction notes
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