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

HRID 512143

Reaktionsgleichung

Br[C:2]1[CH:3]=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.[CH2:12]([O:14][C:15](=[O:19])[CH2:16][C:17]#[N:18])[CH3:13].CC([O-])(C)C.[K+].CC(O)=O>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH2:12]([O:14][C:15](=[O:19])[CH:16]([C:17]#[N:18])[C:2]1[CH:3]=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1)[CH3:13]

Komponenten

Reaktionsbedingungen

Temperatur: 70 °C

Versuchsvorschrift

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).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag: ord-f1c148c0c1e648f48fd5e92dfbacf50d
Quelldatensatz: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09102591B2

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