2-Chloropyridine → 1-(Pyridin-2-yl)piperidin-4-ol

HRID 1958395Notes

Reaction equation

HRID 1958395 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.Cl[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1.CCN(C(C)C)C(C)C>C(O)(C)C>[N:1]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 79772-ChloropyridineHCID 79341Piperidin-4-olHCID 81531Diisopropylethylamine

Product 1

HCID 106074171-(Pyridin-2-yl)piperidin-4-olYield 27.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of piperidin-4-ol (100 mg, 0.99 mmol), desired 2-chloropyridine (0.99 mmol, 1.0 equiv.), and DIPEA (345 μL, 1.98 mmol) in isopropanol (1.5 mL) was heated by microwave irradiation at 160° C. for 2.5 h. The reaction was purified directly by silica gel chromatography to give the desired 3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ol (using 5-bromo-2-chloropyridine, 5′-bromo-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ol was isolated in 27% yield, 69.1 mg, 0.27 mmol; using 5-trifluoromethyl-2-chloropyridine, 5′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-ol was isolated in 62% yield, 150.1 mg, 0.61 mmol).

Workup

  1. customThe reaction was purified directly by silica gel chromatography

Sources & evidence

ORD record
ord-0bc4f486b1614282bf91fc8aa9a9994c
Source dataset
uspto-grants-2013_04
Patent number
US08410119B2

Reaction notes

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