Methyl iodide → 2-[3-(Trifluoromethoxy)phenyl]propanoic acid

Temperature

-70 °C

A solution of diisopropylamine (3.1 ml) in tetrahydrofuran (30 ml) was cooled to 0° C. before dropwise addition of 1.6M nBuLi in hexane (13.5 ml) and then stirred for 15 minutes and cooled to −70° C. 3-(trifluoromethoxy)-phenylacetic acid (2 g) was dissolved in tetrahydrofuran (20 ml) and added dropwise to the reaction mixture which was then allowed to warm to 0° C., stirred for 30 minutes and then cooled back to −70° C. Methyl iodide (0.9 ml) was then added slowly and the solution stirred for further 1.5 hours at −70° C. Water was added the solution washed with diethyl ether, the aqueous phase was acidified by addition of 25% aqueous HCl and then extracted twice with diethyl ether, dried over Mg2SO4, filtered and concentrated. The residue was purified by flash column chromatography (SiO2; hexane/EtOAc 3:1) to afford 2-(3-trifluoromethoxy-phenyl)-propionic acid (1.5 g) as a light yellow oil. MS (ISP): 232.9 ([M−H]+)).

1. additionadded dropwise to the reaction mixture which
2. temperatureto warm to 0° C.
3. stirringstirred for 30 minutes
4. temperaturecooled back to −70° C
5. stirringthe solution stirred for further 1.5 hours at −70° C
6. washwashed with diethyl ether
7. additionthe aqueous phase was acidified by addition of 25% aqueous HCl
8. extractionextracted twice with diethyl ether
9. dry with materialdried over Mg2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by flash column chromatography (SiO2; hexane/EtOAc 3:1)

ORD record

ord-10688b936ce24155a0ba8ed877884c3b

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354441B2