1-(5-Bromopyrimidin-2-yl)piperidin-4-ol → 2-(4-Hydroxypiperidin-1-yl)pyrimidine-5-carbonitrile

HRID 729459Notes

Reaction equation

HRID 729459 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[Cu][C:16]#[N:17]>CN(C=O)C.O.CCOC(C)=O>[OH:14][CH:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:4]=[CH:3][C:2]([C:16]#[N:17])=[CH:7][N:6]=2)[CH2:9][CH2:10]1

Participants

6

Reactant 2

HCID 46411251-(5-Bromopyrimidin-2-yl)piperidin-4-olHCID 178418546HCID 178418546, compound

Product 1

HCID 688212522-(4-Hydroxypiperidin-1-yl)pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 1-(5-bromopyrimidin-2-yl)piperidin-4-ol (5 g, 19.37 mmol) and copper(I) cyanide (6.94 g, 77 mmol) in DMF (48.4 mL) was heated at 140° C. for 18 h. The mixture was diluted with water (100 mL) and EtOAc (50 mL) and filtered through celite. The filtrate was extracted with EtOAc (3×20 mL). The combined organic fractions were washed with 1N HCl (20 mL) then dried over Na2SO4. The solvent was evaporated and the product was recrystallized from CH2Cl2/hexanes, filtered and washed with hexanes to afford the title compound.

Workup

  1. filtrationfiltered through celite
  2. extractionThe filtrate was extracted with EtOAc (3×20 mL)
  3. washThe combined organic fractions were washed with 1N HCl (20 mL)
  4. dry with materialthen dried over Na2SO4
  5. customThe solvent was evaporated
  6. customthe product was recrystallized from CH2Cl2/hexanes
  7. filtrationfiltered
  8. washwashed with hexanes

Sources & evidence

ORD record
ord-be24123cc38d4b0e84e7ae496c01c590
Source dataset
uspto-grants-2009_09
Patent number
US07582633B2

Reaction notes

Loading…