Methyl iodide → Methyl 4-fluoro-alpha-methylbenzeneacetate

A solution of the compound of Example 14A (23.2 g, 0.138 mol) in dry tetrahydrofuran (30 mL) was added dropwise over 30 min to a −78° C. solution of lithium hexamethyldisilazide (prepared from hexamethyldisilazane (35 mL, 0.165 mol) and n-butyllithium in hexane (2.5 M, 58 mL, 0.145 mol)) in dry tetrahydrofuran (100 mL). The solution was stirred at −78° C. for 1 h, and then a large excess of methyl iodide was added. The solution was stirred at −78° C. for 30 min and was then warmed to ambient temperature for 18 h. The solution was quenched by addition of saturated ammonium chloride solution 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, followed by drying (Na2SO4) and concentration in vacuo. The residue was distilled under reduced pressure (70-75° C./0.5 mm Hg) to afford the title compound (21.9 g, 87%) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ 1.49 (d, J=7.35 Hz, 3 H) 3.70 (m, 4 H) 7.01 (m, 2 H) 7.27 (m, 2 H).

1. stirringThe solution was stirred at −78° C. for 30 min
2. temperaturewas then warmed to ambient temperature for 18 h
3. customThe solution was quenched by addition of saturated ammonium chloride solution
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. customby drying
10. concentration(Na2SO4) and concentration in vacuo
11. distillationThe residue was distilled under reduced pressure (70-75° C./0.5 mm Hg)

ORD-Eintrag

ord-bf5dd433bd464e55b9f09e54e13d1740

Quelldatensatz

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07378414B2