2,2,2-Trifluoroethyl trifluoromethanesulfonate → 4-(4-Bromophenyl)-1-(2,2,2-trifluoroethyl)piperidine

Temperature

45 °C

To a mixture of 4-(4-bromophenyl)piperidine hydrochloride (5 g, 18.1 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (4.62 g, 19.9 mmol) in ACN (250 mL) was added N,N-diisopropylethyl amine (11 mL, 63.2 mmol). The reaction mixture was heated at 45° C. for 50 min. 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.46 g, 2.0 mmol) was added and heating continued for 1 h. Another 0.46 g of 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.0 mmol) was added and heating continued for 1 h. The reaction mixture was concentrated, diluted with brine and extracted twice with a mixture of hexanes-EtOAc-DCM. The organic layers were combined, concentrated, diluted with toluene and concentrated again. Purification by flash chromatography on silica gel (0 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 322.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J=8.4 Hz, 2 H),7.08 (d, J=8.4 Hz, 2 H),3.06 (m, 2 H),3.00 (q, J=9.7 Hz, 2 H),2.45 (m, 3 H).1.77 (m, 4H).

1. temperatureheating
2. temperatureheating
3. waitcontinued for 1 h
4. concentrationThe reaction mixture was concentrated
5. additiondiluted with brine
6. extractionextracted twice with a mixture of hexanes-EtOAc-DCM
7. concentrationconcentrated
8. additiondiluted with toluene
9. concentrationconcentrated again
10. customPurification by flash chromatography on silica gel (0 to 100% EtOAc in hexanes)

ORD record

ord-13f4e413cd6b454399b6cdfdea85e8ac

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895583B2