2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 1,1,1,3,3,3-Hexafluoro-2-(4-(2-(3-methoxybenzyl)-4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-2-propanol

Temperature

100 °C

To a 50-mL round-bottomed flask was added 3-(3-methoxybenzyl)-1-(thiophen-2-ylsulfonyl)piperazine (48 mg, 0.14 mmol), tris(dibenzylideneacetone)dipalladium (0) (6 mg, 6.81 μmol, Strem, Newburyport, Mass.), dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (RuPhos) (13 mg, 0.027 mmol, Strem Chemicals, Newburyport, Mass.), sodium tert-butoxide (33 mg, 0.34 mmol) and 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (53 mg, 0.16 mmol, Bioorg. Med. Chem. Lett. 2002, 12, 3009) in toluene (2 mL). The reaction mixture was stirred at 100° C. for 18 h. The mixture was cooled to room temperature and then diluted with saturated aqueous NH4Cl (10 mL) and extracted with EtOAc (2×30 mL). The organic extract was washed with saturated NaCl (10 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as light-yellow oil. The crude product was purified by silica gel chromatography, eluting with 20% EtOAc in hexanes to give 1,1,1,3,3,3-hexafluoro-2-(4-(2-(3-methoxybenzyl)-4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-2-propanol (41 mg) (racemic mixture) as a colorless tar.

1. temperatureThe mixture was cooled to room temperature
2. extractionextracted with EtOAc (2×30 mL)
3. extractionThe organic extract
4. washwas washed with saturated NaCl (10 mL)
5. dry with materialdried over Na2SO4
6. filtrationThe solution was filtered
7. concentrationconcentrated in vacuo
8. customto give the crude material as light-yellow oil
9. customThe crude product was purified by silica gel chromatography
10. washeluting with 20% EtOAc in hexanes

ORD record

ord-e521a7592e564b06b3876e01d43dcb3e

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431563B2