Potassium Carbonate → (3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinol

HRID 841942Notes

Reaction equation

HRID 841942 reaction equation
Cl.[OH:2][C@@H:3]1[CH2:8][CH2:7][CH2:6][NH:5][CH2:4]1.Br[CH2:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]([F:17])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:17][C:13]1[CH:12]=[C:11]([CH2:10][N:5]2[CH2:6][CH2:7][CH2:8][C@@H:3]([OH:2])[CH2:4]2)[CH:16]=[CH:15][N:14]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2759333(3R)-piperidin-3-ol hydrochlorideHCID 139851684-Bromomethyl-2-fluoropyridine

Product 1

HCID 53960603(3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinolYield 88.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3R)-3-hydroxypiperidine hydrochloride (0.188 g) was added to a solution of 4-(bromomethyl)-2-fluoropyridine (0.26 g) [see Porter et al, WO 9622978] and potassium carbonate (0.189 g) in acetonitrile (15 ml). The reaction mixture was refluxed for 5 days, after which time the solvent was removed under reduced pressure and the residue partitioned between dichloromethane and water. The organic layer was separated and the aqueous was adjusted to pH 12 and the product extracted with dichloromethane. The combined organic layers were dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 95:5, by volume, chloroform:methanol to afford (3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinol (0.255 g) as a pale yellow oil.

Workup

  1. temperatureThe reaction mixture was refluxed for 5 days
  2. customafter which time the solvent was removed under reduced pressure
  3. customthe residue partitioned between dichloromethane and water
  4. customThe organic layer was separated
  5. extractionthe product extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried over magnesium sulphate
  7. customthe solvent removed under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 95:5, by volume, chloroform

Sources & evidence

ORD record
ord-372e2e92f4994176933b11063feda96a
Source dataset
uspto-grants-2002_04
Patent number
US06372736B1

Reaction notes

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