Hexane → Methyl 2-(4-fluorophenyl)-2,5,5-trimethylhexanoate

Temperature

25 °C

A solution of the compound of Example 22A (11.75 g, 64.6 mmol) in tetrahydrofuran (30 mL) was added dropwise over 20 min to a −78° C. solution of lithium hexamethyldisilazide (previously prepared from hexamethyldisilazane (17.0 mL, 80.7 mmol) and n-butyllithium in hexane (2.5 M, 31.0 mL, 77.5 mmol)) in tetrahydrofuran (40 mL) and allowed to stir at that temperature for 1 h. The solution was then treated with 1-bromo-3,3-dimethylbutane (12.0 mL, 83.9 mmol), followed by stirring at −78° C. for 30 min, and then warming to 25° C. for 18 h. The solution was quenched by addition of saturated ammonium chloride solution (4 mL) and then concentrated in vacuo. The residue was diluted with ethyl acetate and water. The organic layer was extracted with water (2×), saturated NaCl solution and dried (Na2SO4). Concentration in vacuo afforded an oil, which was distilled under reduced pressure (90-93° C./0.3 mm Hg) to afford the product (4.85 g, 28%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 0.86 (s, 9 H) 1.03 (m, 2 H) 1.51 (m, 3 H) 1.86 (m, 1 H) 2.00 (m, 1 H) 3.65 (m, 3H) 7.03 (m, 2 H) 7.27 (m, 2 H).

1. stirringby stirring at −78° C. for 30 min
2. customThe solution was quenched by addition of saturated ammonium chloride solution (4 mL)
3. concentrationconcentrated in vacuo
4. additionThe residue was diluted with ethyl acetate and water
5. extractionThe organic layer was extracted with water (2×), saturated NaCl solution
6. dry with materialdried (Na2SO4)
7. concentrationConcentration in vacuo
8. customafforded an oil, which
9. distillationwas distilled under reduced pressure (90-93° C./0.3 mm Hg)

ORD record

ord-9470ddfa2f684f9a968c8f2847a0313b

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07538105B2