2-Iodoquinoline → 4-(Hydroxy-quinolin-2-yl-methyl)-4-propyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1895048Notes

Reaction equation

HRID 1895048 reaction equation
I[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C([Mg]Cl)(C)C.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([CH:33]=[O:34])([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>C1COCC1>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([CH:33]([OH:34])[C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)([CH2:30][CH2:31][CH3:32])[CH2:26][CH2:25]1)=[O:23])([CH3:19])([CH3:20])[CH3:18]

Participants

5

Reactant 3

HCID 810442-IodoquinolineHCID 58017246Tert-butyl 4-formyl-4-propylpiperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 580172884-(Hydroxy-quinolin-2-yl-methyl)-4-propyl-piperidine-1-carboxylic acid tert-butyl esterYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-iodoquinoline (670 mg, 2.6 mmol) in THF (10 mL) at 0° C. was slowly added isopropyl magnesium chloride (2.0 M in THF, 1.6 mL, 3.2 mmol). The reaction mixture was stirred at 0° C. for 30 minutes, then a solution of 4-formyl-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (670 mg, 2.6 mmol) in THF (3 mL) was slowly added. The reaction mixture was stirred at 0° C. for 30 minutes, then warmed to room temperature, quenched with saturated aqueous NH4Cl solution, and extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (0% to 20% EtOAc in hexanes) to afford 190 mg (19%) of 4-(hydroxy-quinolin-2-yl-methyl)-4-propyl-piperidine-1-carboxylic acid tert-butyl ester as a yellow oil.

Workup

  1. customat 0° C.
  2. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  3. temperaturewarmed to room temperature
  4. customquenched with saturated aqueous NH4Cl solution
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography (0% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8d7f67850fdb4950acd5f2f631206c45
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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