Benzyl Alcohol → 5-(Benzyloxy)-2-[4-(methanesulfonyl)piperazin-1-yl]pyrimidine

HRID 1723802Notes

Reaction equation

HRID 1723802 reaction equation
I[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH2:18]([OH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.C(Cl)Cl>[CH2:18]([O:25][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 68849595HCID 68849595, compound

Product 1

HCID 688494605-(Benzyloxy)-2-[4-(methanesulfonyl)piperazin-1-yl]pyrimidine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred suspension of 5-iodo-2-[4-(methylsulfonyl)piperazin-1-yl]pyrimidine (25.0 g, 67.9 mmol), benzyl alcohol (125 mL), 1,10-phenanthroline (2.45 g, 20 mol %), and cesium carbonate was added copper (I) iodide (12.9 g, 67.9 mmol) and the reaction heated to 110° C. for 90 minutes then cooled to room temperature. DCM (250 mL) was then added and the insolubles filtered off through a pad of celite. The cake washed with DCM (250 mL) and the DCM filtrates washed with water. The aqueous phase was then back extracted with more DCM (500 mL), the combined DCM extracts washed with brine (500 mL), dried (MgSO4), filtered and concentrated in vacuo to a dark brown sludge. This was then purified by flash chromatography (silica gel, 50% EtOAc/hexanes) to give 5-(benzyloxy)-2-[4-(methylsulfonyl)piperazin-1-yl]pyrimidine as an off white solid (14.2 g, 40.7 mmol, 60%).

Workup

  1. temperaturethen cooled to room temperature
  2. filtrationthe insolubles filtered off through a pad of celite
  3. washThe cake washed with DCM (250 mL)
  4. washthe DCM filtrates washed with water
  5. extractionThe aqueous phase was then back extracted with more DCM (500 mL)
  6. washthe combined DCM extracts washed with brine (500 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a dark brown sludge
  10. customThis was then purified by flash chromatography (silica gel, 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-989f0aafda054a8da71621178447fa62
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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