Reacción #2312004

Ecuación de reacción

hexamethyldisilazane

n-butyllithium

hexane

1-bromo-3,3-dimethylbutane

compound

methyl 2-(4-fluorophenyl)propanoate

lithium hexamethyldisilazide

→

product

Rendimiento 28.0%

methyl 2-(4-fluorophenyl)-2,5,5-trimethylhexanoate

Rendimiento 28.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGby stirring at −78° C. for 30 min
2. 2
   OtroThe solution was quenched by addition of saturated ammonium chloride solution (4 mL)
3. 3
   Concentraciónconcentrated in vacuo
4. 4
   workup.ADDITIONThe residue was diluted with ethyl acetate and water
5. 5
   ExtracciónThe organic layer was extracted with water (2×), saturated NaCl solution
6. 6
   Secadodried (Na2SO4)
7. 7
   ConcentraciónConcentration in vacuo
8. 8
   Otroafforded an oil, which
9. 9
   workup.DISTILLATIONwas distilled under reduced pressure (90-93° C./0.3 mm Hg)

Procedimiento

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, 3 H) 7.03 (m, 2 H) 7.27(m, 2 H).

Fuente