Potassium Hydroxide → 4-(3-TrifluoroMethyl-phenyl)-butyric acid

The intermediate obtained in Step B (2.15 g, 7.07 mmol) was treated with 3.5 mL of a 4.53M solution of methanolic potassium hydroxide (15.9 mmol, 2.2 eq) and the resulting mixture stirred at room temperature for 72 hours. The mixture was concentrated under vacuum and the solid residue redissolved in 4mL of concentrated hydrochloric acid and heated at reflux for 3 hours. The mixture was cooled, then extracted with methylene chloride (3×6mL); the combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was suspended in 20 mL of water and treated with 700 mg (8.3 mmol) of sodium bicarbonate. The solution was washed with ether (2×20 mL); the aqueous phase was removed and acidified (pH 1-2) with 2N HCl. The mixture was extracted with methylene chloride and the combined extracts dried over sodium sulfate, filtered and concentrated under vacuum. The residue was treated with 30 mL of concentrated hydrochloric acid and the mixture heated at reflux for 20 hours. All volatiles were removed under vacuum to afford 1.12 g (4.82 mmol, 68%) of product. 1H NMR (200MHz, CDCl3): 1.98 (m,2H), 2.40 (t,8Hz,2H), 2.74 (t,8Hz,2H), 7.3-7.5 (m,4H).

1. concentrationThe mixture was concentrated under vacuum
2. dissolutionthe solid residue redissolved in 4mL of concentrated hydrochloric acid
3. temperatureheated
4. temperatureat reflux for 3 hours
5. temperatureThe mixture was cooled
6. extractionextracted with methylene chloride (3×6mL)
7. washthe combined extracts were washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. washThe solution was washed with ether (2×20 mL)
12. customthe aqueous phase was removed
13. extractionThe mixture was extracted with methylene chloride
14. dry with materialthe combined extracts dried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated under vacuum
17. additionThe residue was treated with 30 mL of concentrated hydrochloric acid
18. temperaturethe mixture heated
19. temperatureat reflux for 20 hours
20. customAll volatiles were removed under vacuum

ORD record

ord-505ec19748164b6484a518a8893f8666

Source dataset

uspto-grants-1994_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05310737