Methyl iodide → 3,3,3-Trifluoro-2-(methylthiomethyl)propanoic acid

Temperature

65 °C

To a solution of 2-(acetylthiomethyl)-3,3,3-trifluoropropanoic acid (649 mg, 3 mmol) in MeOH (5 mL) stirring at 25° C. was added pellets of potassium hydroxide (421 mg, 7.50 mmol) in four portions over 5 minutes. Reaction was exothermic. Then MeI was added in once, the reaction mixture was then heated at 65° C. for 18 hours. The reaction was then cooled down and quenched with 2N HCl until acidic, and the aqueous layer extracted with chloroform (4×20 mL). Combined organic layer was dried, concentrated in vacuo, purified with flash chromatography (0-20% MeOH/DCM), to give 3,3,3-trifluoro-2-(methylthiomethyl)propanoic acid (410 mg, 2.179 mmol, 72.6% yield) as a light yellow oil: 1H NMR (400 MHz, CDCl3) δ 10.95 (s, 1H), 3.49-3.37 (m, 1H), 3.02 (dd, J=13.8, 10.8 Hz, 1H), 2.90 (dd, J=13.8, 4.0 Hz, 1H), 2.18 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 172.04 (q, J=2.8 Hz), 123.55 (q, J=281.2 Hz), 50.89 (q, J=27.5 Hz), 29.62 (q, J=2.3 Hz), 15.85; 19F NMR (376 MHz, CDCl3) δ −67.98.

1. customReaction
2. temperatureThe reaction was then cooled down
3. customquenched with 2N HCl until acidic, and the aqueous layer
4. extractionextracted with chloroform (4×20 mL)
5. customCombined organic layer was dried
6. concentrationconcentrated in vacuo
7. custompurified with flash chromatography (0-20% MeOH/DCM)

ORD record

ord-455462f94eec4b1ab3778e1229d4dd79

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815271B2