Reaction #50177

Reaction equation

hydrogen

sodium hydride

methyl iodide

4-hydroxy-4-[3-(tetrahydropyran-2-yloxy)-prop-1-ynyl]tetrahydropyran

→

4-methoxy-4-[3-(tetrahydropyran-2-yloxy)prop-1-ynyl]tetrahydropyran

Yield 96.1%

Solvents

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   OtherThe reaction was quenched by addition of crushed ice and saturated aqueous NH4Cl
3. 3
   ExtractionThe resulting two-phase mixture was extracted with ether (3×100 mL)
4. 4
   DryingThe combined organic layers were dried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherPurification by chromatography on silica gel (100 g, 10% ethyl acetate: hexanes)

Procedure

To a suspension of sodium hydride (1.2 g of an 80% oil dispersion, 50 mmol) in dry THF (45 mL) was added a solution of 4-hydroxy-4-[3-(tetrahydropyran-2-yloxy)-prop-1-ynyl]tetrahydropyran(3.71 g, 15.3 mmol), prepared as in step 1. After hydrogen evolution ceased, methyl iodide (3.0 mL, 48.2 mmol) was added neat and the resulting solution was stirred overnight at ambient temperature. The reaction was quenched by addition of crushed ice and saturated aqueous NH4Cl. The resulting two-phase mixture was extracted with ether (3×100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by chromatography on silica gel (100 g, 10% ethyl acetate: hexanes) provided 4-methoxy-4-[3-(tetrahydropyran-2-yloxy)prop-1-ynyl]tetrahydropyran (3.74 g, 95 %) as a colorless oil.

Source