2-Fluoro-5-nitrobenzaldehyde → 4-(Tert-butyldimethylsilyloxy)-1-(2-fluoro-5-nitrophenyl)-2-methylenebutan-1-ol

Temperature

-78 °C

To a solution of (3-bromobut-3-enyloxy)(tert-butyl)dimethylsilane from step A (3.14 g, 11.83 mmol) in THF (10 mL) at −78° C. was added tert-butyllithium (13.91 mL, 23.65 mmol, 1.70 M solution in hexanes) dropwise over a period of 5 min, and the reaction mixture was stirred at −78° C. for 10 min. The resulting lithium reagent was added dropwise to a solution of 2-fluoro-5-nitrobenzaldehyde (2 g, 11.83 mmol) in THF (10 mL) at −78° C., the reaction mixture was stirred at −78° C. for 20 min. The reaction mixture was then partitioned between ethyl acetate and water, and the organic layer was separated and concentrated to a crude product that was purified by chromatography eluting with 0-20% ethyl acetate/hexanes to give a mixture of starting material and the desired product. This mixture was further purified by preparative TLC eluting with 25% EtOAc/hexanes to give the title compound as a colorless oil (941 mg, 22% yield). 1H NMR (500 MHz, CDCl3) δ 8.57 (1H, m), 8.18 (1H, m), 7.15 (1H, m), 5.52 (1H, br. s), 5.16 (1H, s), 5.09 (1H, s), 4.96 (1H, m), 3.7-3.9 (2H, m), 2.20-2.35 (2H, m), 0.97 (9H, s), 0.17 (3H) and 0.15 (3H, s).

1. stirringthe reaction mixture was stirred at −78° C. for 20 min
2. customThe reaction mixture was then partitioned between ethyl acetate and water
3. customthe organic layer was separated
4. concentrationconcentrated to a crude product that
5. customwas purified by chromatography
6. washeluting with 0-20% ethyl acetate/hexanes
7. customto give
8. additiona mixture of starting material

ORD record

ord-da0bb8ae62b94f58afd8721cf58d5649

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598161B2