Reaktion #60665

Reaktionsgleichung

LiCl

tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate

4-(trifluoromethoxy)phenylboronic acid

Na2CO3

→

tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

Ausbeute 52.4%

Lösungsmittel

DME

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturby cooling to room temperature
2. 2
   Einengenconcentrated under reduced pressure
3. 3
   SonstigeThe residue was partitioned between DCM (10 mL), aq Na2CO3 (10 mL, 2N solution) and conc NH4OH (0.6 mL)
4. 4
   SonstigeThe layers were separated
5. 5
   Extraktionthe aqueous layer extracted with DCM (3×10 mL)
6. 6
   TrocknenThe combined organic layers were dried (Na2SO4)
7. 7
   Einengenconcentrated
8. 8
   SonstigePurification by column chromatography (SiO2, Heptane/Ethylacetate/DCM 5:1:1)

Vorschrift

Pd(PPh3)4 (87 mg, 0.0075 mmol), LiCl (190 mg, 4.5 mmol), tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (0.50 g 1.5 mmol), 4-(trifluoromethoxy)phenylboronic acid (0.43 g, 2.1 mmol) and aq Na2CO3 (2 mL, 2N solution) were mixed in 5.2 mL DME and heated at 85° C. for 3 h followed by cooling to room temperature and concentrated under reduced pressure. The residue was partitioned between DCM (10 mL), aq Na2CO3 (10 mL, 2N solution) and conc NH4OH (0.6 mL). The layers were separated and the aqueous layer extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. Purification by column chromatography (SiO2, Heptane/Ethylacetate/DCM 5:1:1) gave tert-butyl 4-[4-(trifluoromethoxy)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate (0.27 g, 52%). The product and 5% Pd/C (30 mg) was mixed in MeOH (3 mL) and stirred under H2 (1 atm) for 24 h. The mixture was filtered through Celite and concentrated to give tert-butyl 4-[4-(trifluoromethoxy)phenyl]piperidine-1-carboxylate (0.23 g, 86%). The crude product was dissolved in a mixture of TFA (2 mL) and DCM (4 mL) and stirred at RT for 2 h. The reaction mixture was concentrated and purified by preparative HPLC to give the title compound (0.14 g, 58%, three steps 26%).

Quelle