((1,1-Dimethyl-2-propynyl)oxy)trimethylsilane → 4-Methyl-1-(thiazol-4-yl)-4-(trimethylsilyloxy)pent-2-yn-1-one

Temperature

-78 °C

To a stirred solution of trimethyl (2-methylbut-3-yn-2-yloxy) silane (0.56 g, 3.57 mmol) in dry THF (10 mL) was added n-BuLi (1.3 mL, 2.1 mmol, 1.6 M in hexane) dropwise at −78° C. under an inert atmosphere for a period of 5 min. After being stirred for 30 min at −78° C., a solution of N-methoxy-N-methylthiazole-4-carboxamide (0.25 g, 1.78 mmol) in dry THF (5 mL) was added to 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 (2×30 mL). The combined organic layers were washed with water (20 mL), brine (20 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 2-4% EtOAc in Hexane to afford 4-methyl-1-(thiazol-4-yl)-4-(trimethylsilyloxy)pent-2-yn-1-one (0.15 g, 31.44%) as an oil.

1. stirringstirring
2. waitwas continued for an additional 1 h at −78° C
3. customThe reaction mixture was quenched with a saturated NH4Cl solution
4. extractionextracted with EtOAc (2×30 mL)
5. washThe combined organic layers were washed with water (20 mL), brine (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto obtain the crude product
10. customThe crude material was purified via silica gel column chromatography
11. washeluting with 2-4% EtOAc in Hexane

ORD record

ord-3b06926ee82447df98120fa635df97f4

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933074B2