Phenolphthalein → Valine, N-[4-(trifluoromethyl)phenyl]-

1.5 Grams (8.3 mmol) of the (S)-2-bromo-3-methylbutanoic acid is titrated with 8 ml of 1 M potassium hydroxide in methanol to a phenolphthalein endpoint. The solution is evaporated under high vacuum at 40° for 1 hour, and 0.51 g (2.33 mmol) of the resulting salt is heated together with 1.52 g (9.43 mmol) of 4-trifluoromethylaniline at 90°-95° under nitrogen for 1 hour. Heating is discontinued and the reaction worked up immediately by partition between ether/5% sodium hydroxide. The layers are separated and the organic phase is extracted with 5% sodium hydroxide (2×). The aqueous layers are combined and washed with ether (2×), then acidified with ice and conc. HCl and extracted with ether (3×). The latter ether extracts are washed with brine, dried over magnesium sulfate, filtered and evaporated, giving (S)-2-(4-trifluoromethylphenylamino)-3-methylbutanoic acid.

1. customThe solution is evaporated under high vacuum at 40° for 1 hour
2. temperatureHeating
3. customby partition between ether/5% sodium hydroxide
4. customThe layers are separated
5. extractionthe organic phase is extracted with 5% sodium hydroxide (2×)
6. washwashed with ether (2×)
7. extractionextracted with ether (3×)
8. washThe latter ether extracts are washed with brine
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. customevaporated

ORD record

ord-d7d15ea46bc049fb80a09c32ba825523

Source dataset

uspto-grants-1981_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04260633