Potassium Phosphate, Tribasic → 3-Cyclopropyl-4-methoxybenzonitrile

Temperatur

80 °C

A mixture of 3-bromo-4-methoxybenzonitrile (5.0 g, 23.6 mmol, 1.0 eq), aqueous potassium phosphate tribasic (65.0 ml, 1.27 M, 3.5 eq), cyclopropylboronic acid (10.1 g, 118 mmol, 5.0 eq), Pd(OAc)2 (0.539 g, 2.36 mmol, 0.1 eq) and tricyclohexylphosphine (0.661 g, 2.36 mmol, 0.1 eq) was stirred in degassed toluene (103 ml) and heated to 80° C. for three hours. An additional amount of cyclopropylboronic acid (1.0 g, 1.16 mmol, 0.5 eq) was added and the solution was further heated for 16 hours at 80° C. to complete the reaction. The reaction mixture was cooled and partitioned between brine and EtOAc. The organic phase was dried over sodium sulfate, filtered and concentrated to give an orange oil. The oil was purified by normal phase column chromatography (0 to 10% EtOAc in hexanes) to afford the product as a yellow oil. 1H NMR (CDCl3) δ 7.44 (dd, 1H, J=8.4, 2.0 Hz), 7.09 (d, 1H, J=2.0 Hz), 6.86 (d, 1H, J=8.4 Hz), 3.92 (s, 3H), 2.13 (m, 1H), 0.97 (m, 2H), 0.65 (m, 2H).

1. temperaturethe solution was further heated for 16 hours at 80° C.
2. customthe reaction
3. temperatureThe reaction mixture was cooled
4. custompartitioned between brine and EtOAc
5. dry with materialThe organic phase was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give an orange oil
9. customThe oil was purified by normal phase column chromatography (0 to 10% EtOAc in hexanes)

ORD-Eintrag

ord-ae4f2c98f52b405c9a0561796238fb85

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08399494B2