Hexamethyldisilazane → Lithium Hexamethyldisilazide

Temperature

-78 °C

a solution of lithium hexamethyldisilazide in tetrahydrofuran (125 mL) was prepared from butyllithium (a 2.77 M hexane solution, 78 mL, 217 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (49 mL, 234 mmol), to which 3-methoxyacrylonitrile (E/Z=5:1, 17 mL, 200 mmol) was slowly added at −78° C. Subsequently, a solution of triisopropylsilyl trifluoromethanesulfonate (45 mL, 167 mmol) in tetrahydrofuran (84 mL) was slowly added through a cannula. After stirring at −78° C. for one hour, a saturated aqueous solution of sodium bicarbonate was added to terminate the reaction. After extraction with diethyl ether, the resulting organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. After concentration, the resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1) to give Compound 4B (32.0 g, 80% based on TIPSOTf) as an inseparable mixture with a ratio of E/Z=24:76. The mixture of the Compound 4B with a ratio of E/Z=24:76 (32.0 g, 134 mmol) thus obtained was dissolved in hexane and then irradiated with a 32 W low pressure mercury lamp at room temperature for four hours in the air. After concentration, the resulting residue was recrystallized from hexane at −30° C. to give Compound 4B as a mono isomer (E-only, 16.6 g, 42%).

1. customto terminate
2. customthe reaction
3. extractionAfter extraction with diethyl ether
4. washthe resulting organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationAfter concentration
7. customthe resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=9/1)

ORD record

ord-25919c03ed1b4a1a904ed238e3d56f67

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759323B2