Water → 1-(5-Propylpyrimidin-2-yl)piperidin-4-ol

HRID 1429523Notes

Reaction equation

HRID 1429523 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.Cl[C:9]1[N:14]=[CH:13][C:12]([CH2:15][CH2:16][CH3:17])=[CH:11][N:10]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:15]([C:12]1[CH:11]=[N:10][C:9]([N:1]2[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]2)=[N:14][CH:13]=1)[CH2:16][CH3:17]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 79341Piperidin-4-olHCID 27357842-Chloro-5-propylpyrimidine

Product 1

HCID 670724781-(5-Propylpyrimidin-2-yl)piperidin-4-olYield 97.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of piperidin-4-ol (5.549 g, 54.9 mmol), 2-chloro-5-propylpyrimidine (8.59 g, 54.9 mmol) and K2CO3 (22.75 g, 165 mmol) in DMF (54.9 mL) was heated to 90° C., where it stirred for 15 hrs. After this time, the reaction mixture was cooled to rt. Once at the prescribe temperature, H2O (80 mL) was added and the resulting mixture was extracted with EtOAc (3×16 mL). The combined organic layers were dried (MgSO4), filtered and then concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 100% EtOAc) to afford 1-(5-propylpyrimidin-2-yl)piperidin-4-ol as a white solid (11.9 g, 97% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 8.15 (s, 2H), 4.40 (dt, J=13.7, 4.4 Hz, 2H), 3.95 (td, J=8.9, 4.7 Hz, 1H), 3.27 (ddd, J=13.3, 10.0, 3.0 Hz, 2H), 2.40 (t, J=7.7 Hz, 2H), 1.87-2.05 (m, 2H), 1.44-1.65 (m, 5H), 0.94 (t, J=7.4 Hz, 3H).

Workup

  1. extractionthe resulting mixture was extracted with EtOAc (3×16 mL)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto yield a residue
  6. customThe residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 100% EtOAc)

Sources & evidence

ORD record
ord-f6edcfd6238b448e94b90f9dd61cf0c0
Source dataset
uspto-grants-2015_01
Patent number
US08940716B2

Reaction notes

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