((1,1-Dimethyl-2-propynyl)oxy)trimethylsilane → 4-(4-Methyl-4-(trimethylsilyloxy)pent-2-ynoyl)benzonitrile

Temperature

-78 °C

To a −78° C. stirred solution of trimethyl (2-methylbut-3-yn-2-yloxy) silane (3.3 g, 20.00 mmol) in dry THF (45 mL), n-BuLi (4.1 mL, 9.00 mmol, 1.6 M in hexane) was added dropwise over 10 minutes under an inert atmosphere. The reaction mixture was stirred for 30 min at −78° C., and then a solution of 4-cyano-N-methoxy-N-methylbenzamide (2.0 g, 10.00 mmol) in dry THF (15 mL) was added to the reaction mixture and stirring was continued for an additional 1 h at −78° C. The reaction mixture was quenched with a saturated NH4Cl solution and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography eluting with 15% EtOAc in hexanes to afford 4-(4-methyl-4-(trimethylsilyloxy)pent-2-ynoyl)benzonitrile (3.8 g, 68%) as a yellow oil.

1. additionwas added dropwise over 10 minutes under an inert atmosphere
2. stirringstirring
3. waitwas continued for an additional 1 h at −78° C
4. customThe reaction mixture was quenched with a saturated NH4Cl solution
5. extractionextracted with EtOAc (2×100 mL)
6. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto obtain the crude product
11. customThe crude material was purified via silica gel column chromatography
12. washeluting with 15% EtOAc in hexanes

ORD record

ord-1ad607ef53994e10847fcf3b6cc5ebeb

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946222B2