2-Pyridinecarboxaldehyde → 2-(4-Bromo-2,6-dimethylphenyl)-5-(hydroxypyridin-2-ylmethyl)-3-methoxycyclopent-2-enone

HRID 514193Notes

Reaction equation

HRID 514193 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[C:10](=[O:16])[CH2:11][CH2:12][C:13]=2[O:14][CH3:15])=[C:4]([CH3:17])[CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[N:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH:34]=[O:35]>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH3:17])[C:5]([C:9]2[C:10](=[O:16])[CH:11]([CH:34]([OH:35])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][N:28]=3)[CH2:12][C:13]=2[O:14][CH3:15])=[C:6]([CH3:8])[CH:7]=1

Participants

5

Reactant 3

HCID 142732-PyridinecarboxaldehydeHCID 2733832Lithium HexamethyldisilazideHCID 668681542-(4-Bromo-2,6-dimethylphenyl)-3-methoxy-cyclopent-2-enone

Product 1

HCID 896011142-(4-Bromo-2,6-dimethylphenyl)-5-(hydroxypyridin-2-ylmethyl)-3-methoxycyclopent-2-enone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-(4-bromo-2,6-dimethylphenyl)-3-methoxycyclopent-2-enone (5 g, 17 mmol) in anhydrous tetrahydrofuran (50 ml) under nitrogen atmosphere is added lithium bis(trimethylsilyl)amide (22.4 ml, 20 mmol, 0.9M solution in tetrahydrofuran) dropwise at −75°C. The resulting solution is stirred at this temperature for 40 minutes, then a second solution of pyridine-2-carboxaldehyde (2.18 g, 20 mmol) in anhydrous tetrahydrofuran (50 ml) is added over 20 minutes. The resulting solution is stirred at −75°C. for 2 hours, then allowed to warm to room temperature and stir for a further 2 hours. The reaction mixture is quenched with ice cold water (30 ml), extracted with ethyl acetate (3×100 ml), then dried over sodium sulfate, filtered and the filtrate is concentrated in vacuo to afford 2-(4-bromo-2,6-dimethylphenyl)-5-(hydroxypyridin-2-ylmethyl)-3-methoxycyclopent-2-enone. This material is used directly in the next step without further purification.

Workup

  1. stirringThe resulting solution is stirred at −75°C. for 2 hours
  2. stirringstir for a further 2 hours
  3. customThe reaction mixture is quenched with ice cold water (30 ml)
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-8c4e75c1234e4f6fa416e0f6bf83ff46
Source dataset
uspto-grants-2015_08
Patent number
US09107415B2

Reaction notes

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