Benzyl Alcohol → 4-(Benzyloxy)-2-chloropyrimidine

HRID 1028059Notes

Reaction equation

HRID 1028059 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[N:17]=[C:16](Cl)[CH:15]=[CH:14][N:13]=1>C1COCC1>[CH2:3]([O:10][C:14]1[CH:15]=[CH:16][N:17]=[C:12]([Cl:11])[N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 775312,4-Dichloropyrimidine

Product 1

HCID 151332374-(Benzyloxy)-2-chloropyrimidineYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (1-2° C.) suspension of sodium hydride (60% in mineral oil) (1.5 equiv) in 250 ml THF, benzyl alcohol (1.0 equiv.) was added dropwise and the mixture stirred 30 min under N2. This suspension was then added in small portions (via syringe, over 1 hr) to a solution of 2,4-dichloropyrimidine (1.5 equiv.) in THF also at 1-2° C. (internal thermometer). The resulting mixture (0.06 M) was stirred at temp <2° C. for 2.5 hrs, then quenched with NH4Cl(sat.) and extracted with EtOAc. Upon separation, the organic layer was washed with NaCl(sat.), dried over Na2SO4, concentrated and purified by silica gel chromatography (hexanes/DCM eluant) to yield 4-(benzyloxy)-2-chloropyrimidine (24%). LC/MS=221.0 (M+H), LC=3.93 min.

Workup

  1. temperatureTo a cooled
  2. additionwas added dropwise
  3. customquenched with NH4Cl(sat.)
  4. extractionextracted with EtOAc
  5. customUpon separation
  6. washthe organic layer was washed with NaCl(sat.)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography (hexanes/DCM eluant)

Sources & evidence

ORD record
ord-6ff6b3c38ef24dd1869ebbe4121c82d2
Source dataset
uspto-grants-2014_05
Patent number
US08735424B2

Reaction notes

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