2-Pyridinecarboxaldehyde → (R)-1-(pyridin-2-ylmethyl)piperidin-3-ol

HRID 841940Notes

Reaction equation

HRID 841940 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([OH:8])[CH2:3]1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH:15]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.O.C(O)(=O)C.C(N(CC)CC)C>[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][N:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([OH:8])[CH2:3]1

Participants

9

Reactant 4

HCID 142732-PyridinecarboxaldehydeHCID 14798Sodium HydroxideHCID 2759333(3R)-piperidin-3-ol hydrochlorideHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 53657319(R)-1-(pyridin-2-ylmethyl)piperidin-3-ol

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Procedure

(3R)-3-Piperidinol hydrochloride (10.0 g) and triethylamine (10.13 ml) in dry 1,2-dichloroethane (350 ml) were stirred for 15 minutes at 50° C. 2-Pyridine carboxaldehyde (7.63 ml) and glacial acetic acid (4.16 ml) were added and the reaction mixture stirred for 1.5 hours at reflux. Sodium triacetoxyborohydride (34.65 g) was then added portionwise and the resulting mixture was cooled to room temperature and stirred for a further 1 hour. Water (350 ml) and 1M aqueous sodium hydroxide solution were then added until the mixture was pH12. The organic layer was separated and the aqueous extracted with chloroform, the combined organic layers were dried over magnesium sulphate and the solvent was 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-pyridinylmethyl)-3-piperidinol (8.10 g) as a brown oil.

Workup

  1. temperatureat reflux
  2. stirringstirred for a further 1 hour
  3. customThe organic layer was separated
  4. extractionthe aqueous extracted with chloroform
  5. dry with materialthe combined organic layers were dried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. 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-86f5f0861c2547c0aa0cbbad61171883
Source dataset
uspto-grants-2002_04
Patent number
US06372736B1

Reaction notes

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