2-Chloroquinoline → 1-Benzyl-4-(2-chloroquinolin-3-yl)piperidin-4-ol

HRID 1695915Notes

Reaction equation

HRID 1695915 reaction equation
[Li+].CC([N-]C(C)C)C.[Cl:9][C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1.[CH2:20]([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1COCC1>[CH2:20]([N:27]1[CH2:32][CH2:31][C:30]([C:19]2[C:10]([Cl:9])=[N:11][C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)([OH:33])[CH2:29][CH2:28]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 119282-ChloroquinolineHCID 192201-Benzyl-4-piperidoneHCID 2724682Lithium diisopropylamide

Product 1

HCID 184442481-Benzyl-4-(2-chloroquinolin-3-yl)piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-20 °C

Procedure

To a solution of LDA (3.4 ml of 2 M in Hept/THF) at −78° C. in THF (5 ml) was added a solution of 2-chloroquinoline (1.0 g. 6.11 mmol) in THF (10 ml) dropwise, and the reaction mixture stirred at −78° C. for 1 hour before a solution of 1-benzylpiperidin-4-one (1.22 g, 6.22 mmol) in THF (2 ml) was added dropwise. The reaction mixture was stirred from −78° C. to RT over two hours, cooled to −20° C., quenched with water and extracted with EtOAc. The organics combined, dried (Na2SO4) and evaporated to dryness. Purification by column chromatography (1 to 15% MeOH in DCM) gave the desired product. LC/MS (10% to 99%): M/Z (M+H)+ (obs)=353; tR=2.24.

Workup

  1. additionwas added dropwise
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. dry with materialdried (Na2SO4)
  5. customevaporated to dryness
  6. customPurification by column chromatography (1 to 15% MeOH in DCM)

Sources & evidence

ORD record
ord-7c3ca17e404b4f1db4bd0100154c473a
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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