Tetrahydrofuran → 1-Benzyl-4-(2-chloro-6-methoxyquinolin-3-yl)piperidin-4-ol

HRID 74561Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[N:3]=1.C([N-]C(C)C)(C)C.[Li+].[CH2:22]([N:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C:30]1=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C[O:39]CC1>>[CH2:22]([N:29]1[CH2:34][CH2:33][C:32]([C:11]2[C:2]([Cl:1])=[N:3][C:4]3[C:9]([CH:10]=2)=[CH:8][C:7]([O:12][CH3:13])=[CH:6][CH:5]=3)([OH:39])[CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

Reactant 4

HCID 8028Tetrahydrofuran2×

HCID 836472-Chloro-6-methoxyquinoline

HCID 2724682Lithium diisopropylamide

HCID 51700761-Benzyl-2-piperidone

Product 1

HCID 581811261-Benzyl-4-(2-chloro-6-methoxyquinolin-3-yl)piperidin-4-ol

Conditions

Temperature: -78 °C

Procedure

Under an argon atmosphere 5.0 g (25 mmol) 2-chloro-6-methoxyquinoline in a small amount of THF were added dropwise at −78° C. to 14 mL (28 mmol) of a 2 M lithium diisopropylamide solution (in THF) in 50 mL THF. Then the mixture was stirred for 1.5 h at −78° C. and 4.5 mL (25 mmol) N-benzylpiperidone was added dropwise. The mixture was stirred for a further 15 min with cooling before slowly being heated to RT. The reaction mixture was stirred overnight, evaporated down and purified by flash chromatography on aluminium oxide. The product-containing fractions were combined and evaporated down.

Workup

stirringThe mixture was stirred for a further 15 min
temperaturewith cooling
temperaturebefore slowly being heated to RT
stirringThe reaction mixture was stirred overnight
customevaporated down
custompurified by flash chromatography on aluminium oxide
customevaporated down

Sources & evidence

ORD record: ord-9443c894840b43aa8c4008ecd5502c39
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829006B2

Reaction notes

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