Sodium Iodide → 1-(4-Trifluoromethylpyrimidin-5-yl)-1-(4-methoxypyrimidin-5-yl)-1-benzyloxymethane

HRID 861393Notes

Reaction equation

HRID 861393 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[C:8]([CH:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[N:15][CH:16]=2)[OH:10])=[CH:7][N:6]=[CH:5][N:4]=1.[H-].[Na+].[Na+].[I-].[CH2:25](Cl)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1.CCCCCC.CCOC(C)=O.CN(C)C=O>[F:20][C:2]([F:1])([F:19])[C:3]1[C:8]([CH:9]([C:11]2[C:12]([O:17][CH3:18])=[N:13][CH:14]=[N:15][CH:16]=2)[O:10][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:7][N:6]=[CH:5][N:4]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 197028001-(4-Trifluoromethylpyrimidin-5-yl)-1-(4-methoxypyrimidin-5-yl)methanol

Product 1

HCID 197027931-(4-Trifluoromethylpyrimidin-5-yl)-1-(4-methoxypyrimidin-5-yl)-1-benzyloxymethaneYield 52.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 21226206Ethyl acetate hexaneSolvent2×

Procedure

1-(4-trifluoromethylpyrimidin-5-yl)-1-(4-methoxypyrimidin-5-yl)methanol (56 mg, 0.196 mmol) in THF (2.5 ml) was added dropwise to a suspension of NaH (12 mg, 0.40 mmol, 80% in mineral oil) in THF (0.5 ml) at ice-bath temperature and stirred for 45 minutes. NaI (56 mg, 0.37 mmol) was then added as a solid and benzyl chloride (50 μl, 54 mg, 0.90 mmol, 2.25 equivalent) via syringe. Dimethyl formamide (DMF) (0.5 ml) was added and the solution was allowed to warm to room temperature. When the reaction was complete, as determined by TLC (SiO2 ; hexane/EtOAc, 1:1), it was quenched with 30% aqueous HOAc, diluted with water and extracted with EtOAc (3 times). The combined extracts were washed with brine (sat.), dried (MgSO4), filtered and concentrated in vacuo to give 66 mg of crude material. Preparative thin layer chromatography (SiO2 ; hexane/EtOAc, 1:1) afforded 39 mg of 1-(4-trifluoromethylpyrimidin-5-yl)-1-(4-methoxypyrimidin-5-yl)-1-benzyloxymethane as an oil.

Workup

  1. customwas quenched with 30% aqueous HOAc
  2. additiondiluted with water
  3. extractionextracted with EtOAc (3 times)
  4. washThe combined extracts were washed with brine (sat.)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give 66 mg of crude material

Sources & evidence

ORD record
ord-48922be63d0f48018a8a844d2c4a5c60
Source dataset
uspto-grants-1998_02
Patent number
US05714438

Reaction notes

Loading…