Trichloroacetonitrile → Methyl 2-fluoro-4-{5-[2'-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

HRID 219907Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 219907
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC(Cl)(Cl)C#N.[NH2:45][C:46](=[N:58]O)[C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[C:49]([F:57])[CH:48]=1.CCN(C(C)C)C(C)C>C1COCC1>[F:57][C:49]1[CH:48]=[C:47]([C:46]2[N:45]=[C:13]([C:12]3[CH:11]=[CH:10][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[C:2]([F:1])([F:19])[F:18])=[CH:17][CH:16]=3)[O:15][N:58]=2)[CH:56]=[CH:55][C:50]=1[C:51]([O:53][CH3:54])=[O:52]

Komponenten

7

Edukt 5

HCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 27827142'-Trifluoromethyl (1,1'-biphenyl)-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

Produkt 1

HCID 67529078Methyl 2-fluoro-4-{5-[2'-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoateAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a microwave vial were added 4-(2-trifluoromethylphenyl)benzoic acid (Fluorochem, 53.2 mg; 0.20 mmol; 1 eq.), triphenylphosphine polymer bound (375 mg; 0.60 mmol; 3 eq.) and trichloroacetonitrile (30 μl; 0.30 mmol; 1.50 eq.). Anhydrous THF (2 mL) was added and the reaction vessel was sealed and heated to 100° C. for 5 min in the microwave. After cooling, the reaction vessel was uncapped and without filtering, Intermediate 1 (46.7 mg; 0.22 mmol; 1.10 eq.) in anhydrous THF (2 mL) was added to the solution along with DIEA (69 μl; 0.40 mmol; 2 eq.). The reaction was capped and heated at 150° C. for 15 min. After cooling, the reaction vessel was uncapped again and the resin was filtered, the filtrate passed through an NH2 SPE column (2 g) and washed by additional THF (2×2 mL). Solvents were evaporated, affording the title compound as a brown solid (61.9 mg; 70%). It was used in the next step without further purification. LC/MS (Method A): 443.3 (M+H)+. HPLC (Method A), Rt 5.98 min (Purity: 87.9%).

Aufarbeitung

  1. customthe reaction vessel was sealed
  2. temperatureAfter cooling
  3. filtrationwithout filtering
  4. customThe reaction was capped
  5. temperatureheated at 150° C. for 15 min
  6. temperatureAfter cooling
  7. filtrationthe resin was filtered
  8. washwashed by additional THF (2×2 mL)
  9. customSolvents were evaporated

Quellen und Nachweise

ORD-Eintrag
ord-cf38cb242a1d4de1b3521303a53bc788
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202865B2

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