Sodium Carbonate → 1-(2-Chloro-5-methyl-4-pyrimidinyl)-4-piperidinol

HRID 603497Notes

Reaction equation

HRID 603497 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH3:9])=[CH:4][N:3]=1.[NH:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1.C([O-])([O-])=O.[Na+].[Na+]>CCO>[Cl:1][C:2]1[N:7]=[C:6]([N:10]2[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]2)[C:5]([CH3:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 79341Piperidin-4-ol

Product 1

HCID 593004611-(2-Chloro-5-methyl-4-pyrimidinyl)-4-piperidinolYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 2,4-dichloro-5-methylpyrimidine (5.0 g, 30.7 mmol) in EtOH (100 mL) were added 4-piperidinol (3.1 g, 30.7 mmol) and Na2CO3 (16.3 g, 153.4 mmol). The reaction mixture was stirred at rt for 72 h, after which the reaction mixture was filtered through Celite®. The filtrate was then concentrated under reduced pressure, the residue dissolved in EtOAc, and the organic solution washed with water and brine after which it was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then purified by silica gel flash chromatography (1:1 EtOAc/hexanes to 100% EtOAc) to give the product (4.8 g, 90%) as a white waxy solid. 1H NMR (400 MHz, CDCl3) δ 1.62-1.70 (m, 2H), 1.70 (d, 1H), 1.98-2.03 (m, 2H), 2.21 (s, 3H), 3.22-3.28 (m, 2H), 3.87-3.92 (m, 2H), 3.97-3.98 (m, 1H), 7.92 (s, 1H).

Workup

  1. filtrationafter which the reaction mixture was filtered through Celite®
  2. concentrationThe filtrate was then concentrated under reduced pressure
  3. dissolutionthe residue dissolved in EtOAc
  4. washthe organic solution washed with water and brine after which it
  5. dry with materialwas dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was then purified by silica gel flash chromatography (1:1 EtOAc/hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-9a7a396819334a049550cd3d2910d547
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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