Tetrahydrofuran → Methyl 2-(2-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetate

HRID 705734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 705734
I[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([S:12][CH3:13])[N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[CH2:41][C:42]([O:44][CH3:45])=[O:43])#[CH:34].C1COCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[CH3:13][S:12][C:4]1[N:3]=[C:2]([C:34]#[C:33][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[CH2:41][C:42]([O:44][CH3:45])=[O:43])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=1

Komponenten

8

Edukt 4

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 717433934-Iodo-2-(methylthio)-5-(trifluoromethyl)pyrimidine

Produkt 1

HCID 68282774Methyl 2-(2-((2-(methylthio)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetateAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

4-Iodo-2-(methylthio)-5-(trifluoromethyl)pyrimidine (I12) (2.00 g, 6.24 mmol), PdCl2(PPh3)2 (438 mg, 625 μmol), CuI (119 mg, 625 μmol) and triphenylphosphine (164 mg, 625 μmol) were placed into an oven dried microwave reaction vial under nitrogen. Methyl 2-(2-ethynylphenyl)acetate (I4) (131 g, 7.49 mmol), THF (20 mL) and triethylamine (10 mL) were added and the resulting mixture was stirred at 100° C. under microwave irradiation for 10 min. The volatiles were evaporated under reduced pressure then the residue was adsorbed onto silica from DCM. The pre-adsorbed material was chromatographed on silica gel (0-25% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I13) (1.571 g, 69%) as an orange solid; 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J=0.8 Hz, 1H), 7.68 (dd, J=7.7, 1.1 Hz, 1H), 7.50-7.29 (m, 3H), 3.93 (s, 2H), 3.71 (d, J=3.4 Hz, 3H), 2.62 (d, J=3.4 Hz, 3H).

Aufarbeitung

  1. customdried
  2. custommicrowave reaction vial under nitrogen
  3. customThe volatiles were evaporated under reduced pressure
  4. customThe pre-adsorbed material was chromatographed on silica gel (0-25% ethyl acetate/petroleum benzine 40-60° C.)

Quellen und Nachweise

ORD-Eintrag
ord-8eb2e009b7f74928b8d3f57c8279cfeb
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174946B2

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