tert-Butyl 4-formylpiperidine-1-carboxylate → tert-Butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate

HRID 928784Notes

Reaction equation

HRID 928784 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Cl)(C)C.[CH:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:14]>C1COCC1>[OH:14][CH:13]([C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1)[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 178418918HCID 178418918, compound

Product 1

HCID 86715620tert-Butyl 4-(hydroxy(1-methyl-1H-imidazol-5-yl)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-bromo-1-methyl-1H-imidazole (25.0 g, 155 mmol; dried over 3 Å molecular sieves, then filtered) in DCM (310 mL) was stirred on an ice bath while iPrMgCl (72 mL, 2.01 M solution in THF, 145 mmol) was added rapidly dropwise under argon via pressure-equalizing addition funnel. Residual iPrMgCl was rinsed down with 50 mL THF, and the ice bath was removed and the reaction stirred for 25 minutes. A solution of tert-butyl 4-formylpiperidine-1-carboxylate (27.6 g, 130 mmol) (PharmaCore) in THF (65 mL) was added dropwise over ˜5 minutes via pressure-equalizing addition funnel at room temperature. After stirring 1 hour at room temperature, the yellow mixture was quenched with 5 M aqueous NH4Cl (250 mL) in one portion. The organic layer was dried (Na2SO4), filtered, and concentrated to provide the crude title compound as a clear light amber oil.

Workup

  1. customdried over 3 Å molecular sieves
  2. filtrationfiltered) in DCM (310 mL)
  3. additionwas added rapidly dropwise under argon via pressure-equalizing addition funnel
  4. washResidual iPrMgCl was rinsed down with 50 mL THF
  5. customthe ice bath was removed
  6. stirringAfter stirring 1 hour at room temperature
  7. customthe yellow mixture was quenched with 5 M aqueous NH4Cl (250 mL) in one portion
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f6ce232661874ebc870a448e17daefa6
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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