Diisopropylamine → 2-[[(Phenylmethyl)thio]methyl]-4,4,4-trifluorobutyric acid

Temperature

0 °C

To a solution of lithium diisopropylamide [prepared using freshly distilled diisopropylamine (4.47 g., 44.4 mmol) and n-butyl lithium/hexane (18 mL, 45 mmol, 2.5M)]in dry tetrahydrofuran (35 mL) was added a solution of 4,4,4-trifluorobutyric acid (3.0 g., 21.0 mmol) in tetrahydrofuran (25 mL). After stirring at 0° C. for 1.5 hours, the solution was cooled to -78° C. and treated with a solution of benzyl bromomethyl thioether in tetrahydrofuran (10 mL). The solution was allowed to stir overnight as the temperature rose to ambient. Volatiles were removed in vacuo and the residue was dissolved in ethyl acetate and extracted with 1N sodium hydroxide (50 mL) and water (2 x 20 mL). The combined basic extracts were acidified with concentrated hydrochloric acid (8 mL) and extracted with ethyl acetate (2×100 mL). The organic extracts were washed with water and brine, combined, dried (MgSO4), and concentrated in vacuo to give 3.82 g. of an oil. Flash chromatography on 350 mL of silica gel and elution with ethyl acetate:hexanes: acetic acid, 50:100:1 gave 1.36 g. of the title A product, TLC Rf =0.38 (ethyl acetate:hexanes:acetic acid, 50:50:1).

1. temperaturethe solution was cooled to -78° C.
2. stirringto stir overnight as the temperature
3. customVolatiles were removed in vacuo
4. dissolutionthe residue was dissolved in ethyl acetate
5. extractionextracted with 1N sodium hydroxide (50 mL) and water (2 x 20 mL)
6. extractionextracted with ethyl acetate (2×100 mL)
7. washThe organic extracts were washed with water and brine
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customto give 3.82 g
11. washFlash chromatography on 350 mL of silica gel and elution with ethyl acetate
12. customhexanes: acetic acid, 50:100:1 gave 1.36 g

ORD record

ord-86502abcd25c4c018f3728f4cb355a79

Source dataset

uspto-grants-1995_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05414013