Trimethylsilylacetylene → 1-Fluoro-4-(trimethylsilyl)but-3-YN-2-one

Temperatur

0 °C

A 0° C. solution of trimethylsilylacetylene (42.0 g, 429 mmol) in THF (400 mL) was treated with n-BuLi (2.5 M in n-hexane; 171 mL, 428 mmol) over 20 min maintaining the internal temperature below 10° C. using dry ice-acetone bath (−20° C.). After stirring for 30 min at 0° C., the mixture was treated with a solution of 2-fluoro-1-morpholin-4-yl-ethanone (8, 48.4 g, 329 mmol) in THF (50 mL+10 mL for wash), and stirring was continued for further 1 h at 0° C. The reaction was quenched by adding to a 0° C. mixture of acetic acid (250 mL) and water (150 mL) over 1 h maintaining the internal temperature below 5° C. After addition of more water (150 mL), the organic layer was separated, washed with water (200 mL), and dried over anhydrous MgSO4, and concentrated in vacuo. The residue was evaporated again with toluene (200 mL) to remove the residual acetic acid, and vacuum distillated (8 mbar, b.p. 54° C.) to give the title compound (33.7 g, 64.8%). 1H NMR (500 MHz, CDCl3) δ 4.90 (d, J=47.1 Hz, 2H), 0.26 (s, 9H). 13C NMR (125 MHz, CDCl3) d 181.0 (d, J=21.5 Hz), 104.0, 98.1, 84.8 (d, J=187 Hz).

1. temperaturemaintaining the internal temperature below 10° C.
2. custom(−20° C.)
3. stirringstirring
4. waitwas continued for further 1 h at 0° C
5. customThe reaction was quenched
6. additionby adding to a 0° C.
7. additionmixture of acetic acid (250 mL) and water (150 mL) over 1 h
8. temperaturemaintaining the internal temperature below 5° C
9. additionAfter addition of more water (150 mL)
10. customthe organic layer was separated
11. washwashed with water (200 mL)
12. dry with materialdried over anhydrous MgSO4
13. concentrationconcentrated in vacuo
14. customThe residue was evaporated again with toluene (200 mL)
15. customto remove the residual acetic acid, and vacuum

ORD-Eintrag

ord-2b9e12df10644c528a4062894bb9e874

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07906676B2