Phenylacetylene → 2-(4-Cyclopentylamino-phenyl)-1,1,1-trifluoro-4-phenyl-but-3-yn-2-ol

Temperature

-78 °C

To a solution of 0.4 ml of phenylacetylene (3.6 mmol in 10 ml of THF at −78° C. was added 1.9 ml (4.75 mmol) of a 2.5 M solution of n-butyllithium in hexanes. The color of the solution turned dark blue and the reaction mixture was stirred at −78° C. for 30 min. After this time, a solution of 450 mg of 1-(4-cyclopentylamino-phenyl)-2,2,2-trifluoro-ethanone (1.75 mmol) in 2 ml of THF was added and the resultant mixture stirred at −78° C. for 1.5 h before being allowed to warn to room temperature and stirred for a further 14 h. After this time, the reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and the filtrate was concentrated. The residue was purified by chromatography on silica (hexanes:EtOAc, 3:1) to give the title compound. 1H-NMR (CDCl3) δ 1.48–1.56 (m, 2H), 1.68–1.76 (m, 4H), 2.03–2.14 (m, 2H), 3.76–3.85 (m, 1H), 6.65 (d, J=8.6 Hz, 2H), 7.36–7.82 (m, 10H). Mass Spectrum (CI+) m/e=360.1 (M+1).

1. customto warn to room temperature
2. stirringstirred for a further 14 h
3. customAfter this time, the reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride
4. extractionextracted with EtOAc
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationthe filtrate was concentrated
9. customThe residue was purified by chromatography on silica (hexanes:EtOAc, 3:1)

ORD record

ord-905bcbd6cf02468cae9f1104f7cb26a1

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07071358B2