Acetic Acid → Cyano-(2-trifluoromethyl-pyrimidin-5-yl)-acetic acid ethyl ester

Temperatur

70 °C

A mixture of 5-bromo-2-trifluoromethyl-pyrimidine (1.0 g, 4.41 mmol) and cyano-acetic acid ethyl ester (1.0 g, 4.41 mmol) was added into a suspension of t-BuOK (17.64 mL, 17.64 mmol, 1M in THF) in 1,4-dioxane (10 mL) under Ar atmosphere. To the resulting mixture was added a solution of Pd(OAc)2 (10 mg, 44.1 μmol) and dppf (48.9 mg, 88.2 μmol) in 1,4-dioxane (1 mL). The resulting mixture was heated to 70° C. for 1 h. The reaction mixture was adjusted pH to 7˜8 with 1N AcOH and extracted with EtOAc (3×20 ml). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (EtOAc:petroleum ether=1:10) to give cyano-(2-trifluoromethyl-pyrimidin-5-yl)-acetic acid ethyl ester (140 mg, yield: 12.3%). 1H NMR (CDCl3 400 Hz): δ9.03 (s, 2H), 4.88 (s, 1H), 4.34 (q, J=7.2 Hz, 2H), 1.35 (t, J=7.2 Hz, 3H).

1. extractionextracted with EtOAc (3×20 ml)
2. dry with materialThe organic layer was dried over Na2SO4
3. concentrationconcentrated
4. customThe residue was purified by column chromatography on silica gel (EtOAc:petroleum ether=1:10)

ORD-Eintrag

ord-f1c148c0c1e648f48fd5e92dfbacf50d

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09102591B2