1-Bromo-3-methylbutane → Methyl 2-(4-fluorophenyl)-2,5-dimethylhexanoate

Temperature

-78 °C

A solution of the compound of Example 22A (10.0 g, 55 mmol) in tetrahydrofuran (30 mL) was added dropwise over 30 min to a −78° C. solution of lithium hexamethyldisilazide (prepared from hexamethyldisilazane (14.5 mL, 68.7 mmol) and n-butyllithium in hexane (2.5 M, 26.4 mL, 65.9 mmol)). The solution was stirred at −78° C. for 1 h. The solution was then treated with neat isoamyl bromide (9.9 mL, 82.4 mmol) followed by stirring at −78° C. for 30 min, and then warming to ambient temperature for 48 h. The solution was quenched by addition of saturated ammonium chloride solution (6 mL) and diluted with water. The mixture was concentrated in vacuo to remove tetrahydrofuran, and then extracted with ethyl acetate. The organic layer was extracted with water (2×) and saturated NaCl solution. Drying (Na2SO4) and concentration in vacuo afforded a brown oil, which was distilled under reduced pressure (90-93° C./0.3 mm Hg) to afford the title compound (11.8 g, 85%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 0.87 (m, 6 H) 1.03 (m, 2 H) 1.51 (m, 4 H) 1.95 (m, 2 H) 3.65 (s, 3 H) 7.01 (m, 2 H) 7.28 (m, 2 H).

1. stirringby stirring at −78° C. for 30 min
2. temperaturewarming to ambient temperature for 48 h
3. customThe solution was quenched by addition of saturated ammonium chloride solution (6 mL)
4. additiondiluted with water
5. concentrationThe mixture was concentrated in vacuo
6. customto remove tetrahydrofuran
7. extractionextracted with ethyl acetate
8. extractionThe organic layer was extracted with water (2×) and saturated NaCl solution
9. customDrying
10. concentration(Na2SO4) and concentration in vacuo
11. customafforded a brown oil, which
12. distillationwas distilled under reduced pressure (90-93° C./0.3 mm Hg)

ORD record

ord-f6551594a83843f992c73061fc5cc160

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378414B2