4-Chlorophenylboronic acid → Ethyl 5-(4-chlorophenyl)thiophene-2-carboxylate

Temperatur

100 °C

A mixture of ethyl 5-bromothiophene-2-carboxylate (1.0 g, 4.25 mmol), 4-chlorophenylboronic acid (0.998 g, 6.38 mmol), 2.0 M aq NaHCO3 (6.38 ml, 12.76 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.492 g, 0.425 mmol) in DMF (40 ml) under nitrogen was stirred at 100° C. under nitrogen in a sealed tube for 18 hours as described in WO 2007/011284. The reaction was then cooled to RT, diluted with saturated aq NaHCO3 (40 ml) and extracted with EtOAc (40 ml). The EtOAc extracts were dried over Na2SO4 and concentrated. The crude product was purified by ISCO chromatography on a silica gel column (120 g) employing a 10 min gradient ranging from hexane to 30% EtOAc to elute ethyl 5-(4-chlorophenyl)thiophene-2-carboxylate (1.05 g, 3.94 mmol, 93% yield) as a white solid. LC MS at t=2.70 min. (m+H=267) Phenomenex S5 C18 4.6×30 mm column/water-MeOH-TFA 90:10:0.1 to 10:90:0.1 gradient over 2 min at 5 mL/min with 1 min hold at the end of the gradient. 1H NMR (400 MHz, CD3OD) δ ppm 1.39 (t, J=7.18 Hz, 3H), 4.37 (q, J=7.22 Hz, 2H), 7.43-7.51 (m, 3H), 7.71 (d, J=8.56 Hz, 2H), 7.78 (d, J=4.03 Hz, 1H).

1. temperatureThe reaction was then cooled to RT
2. extractionextracted with EtOAc (40 ml)
3. dry with materialThe EtOAc extracts were dried over Na2SO4
4. concentrationconcentrated
5. customThe crude product was purified by ISCO chromatography on a silica gel column (120 g)
6. waitemploying a 10 min

ORD-Eintrag

ord-b24b44e8a40046a3aa50dad65e23020a

Quelldatensatz

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07851622B2