Water → HCID 86628337, compound

HRID 21338Notes

Reaction equation

HRID 21338 reaction equation
[Br:1][C:2]1[N:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]([CH3:15])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:8])=[O:5].[Li+].CC([N-]C(C)C)C.CCCCCCC.C1C[O:38][CH2:37]C1.C(C1C=CC=CC=1)C.CN(C=O)C.O>C1COCC1>[Br:1][C:2]1[C:3]2[C:4](=[O:5])[N:6]([C:7]([CH3:15])([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH3:8])[CH:37]([OH:38])[C:16]=2[CH:17]=[CH:18][N:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 86590273LDA THF ethylbenzene heptaneHCID 866283362-bromo-N-(1-methyl-1-phenylethyl)nicotinamide

Product 1

HCID 86628337HCID 86628337, compoundYield 25.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Bromo-N-(1-methyl-1-phenylethyl)nicotinamide (500 mg, 1.57 mmol) was dissolved in THF (20 mL), and the solution was added with LDA-heptane/THF/ethylbenzene solution (2.0 mol/L, 3.5 mL, 7.1 mmol) by drops at −78° C. for 25 minutes under argon atmosphere, followed by stirring at the same temperature for 1.6 hours. Then, the mixture was added with DMF (0.267 mL, 3.45 mmol) and warmed from −78° C. to room temperature over 1 hour. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography (chloroform/methanol=100/1 to 97/3) to obtain 4-bromo-1-hydroxy-2-(1-methyl-1-phenylethyl)-1,2-dihydropyrrolo[3,4-c]pyridine-3-one (138 mg, yield 25%).

Workup

  1. temperaturewarmed from −78° C. to room temperature over 1 hour
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by flash column chromatography (chloroform/methanol=100/1 to 97/3)

Sources & evidence

ORD record
ord-cda688a316bd420eb4294ebce63fa3f3
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Reaction notes

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