Piperidin-4-ol → 1-(3-Chloro-5-fluoro-4-pyridyl)piperidin-4-ol

HRID 524904Notes

Reaction equation

HRID 524904 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:9])[C:7]=1I.CCN(C(C)C)C(C)C.[NH:19]1[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]1>CN1C(=O)CCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:9])[C:7]=1[N:19]1[CH2:24][CH2:23][CH:22]([OH:25])[CH2:21][CH2:20]1

Participants

6

Reactant 3

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 110325453-Chloro-5-fluoro-4-iodopyridine

Product 1

HCID 867209601-(3-Chloro-5-fluoro-4-pyridyl)piperidin-4-ol

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-chloro-5-fluoro-4-iodo-pyridine (1 g, 3.885 mmol) in NMP (1 mL) was added DIPEA (753.1 mg, 1.015 mL, 5.828 mmol) and piperidin-4-ol (589.4 mg, 5.828 mmol) and the mixture heated to 120° C. for 4 hours. The mixture was diluted with ethyl acetate (30 ml), washed twice with water (20 ml) and with brine. The organic layer was dried with MgSO4 and concentrated in vacuo to a yellow solid that was purified by column chromatography using DCM and then 2% MeOH/DCM as eluent, yielding 1-(3-chloro-5-fluoro-4-pyridyl)piperidin-4-ol. MS (ES+) 231.0.

Workup

  1. washwashed twice with water (20 ml) and with brine
  2. dry with materialThe organic layer was dried with MgSO4
  3. concentrationconcentrated in vacuo to a yellow solid
  4. customthat was purified by column chromatography

Sources & evidence

ORD record
ord-ca8aac4f5de04a68bae78c35d1f8096e
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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