Dichloromethane → (E)-5-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-one

HRID 1503791Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1503791
[F:1][C:2]([F:35])([F:34])[CH:3]([C:25]1[CH:30]=[C:29](Cl)[C:28]([Cl:32])=C(Cl)[CH:26]=1)/[CH:4]=[CH:5]/[C:6]1[CH:20]=[CH:19][C:9]([C:10]([NH:12][C:13]2([C:16]([OH:18])=O)[CH2:15][CH2:14]2)=[O:11])=[C:8]([C:21]([F:24])([F:23])[F:22])[CH:7]=1.CCN=C=NCCCN(C)C.[ClH:47].Cl[CH2:49][Cl:50]>>[F:34][C:2]([F:1])([F:35])[CH:3]([C:25]1[CH:30]=[C:29]([Cl:47])[C:28]([Cl:32])=[C:49]([Cl:50])[CH:26]=1)/[CH:4]=[CH:5]/[C:6]1[CH:20]=[CH:19][C:9]([C:10]2[O:11][C:16](=[O:18])[C:13]3([CH2:15][CH2:14]3)[N:12]=2)=[C:8]([C:21]([F:24])([F:23])[F:22])[CH:7]=1

Komponenten

4

Edukt 3

HCID 6344DichloromethaneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86722602(E)-1-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylic acid

Produkt 1

HCID 86722601(E)-5-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)phenyl)-6-oxa-4-azaspiro[2.4]hept-4-en-7-oneAusbeute 73 %

Versuchsvorschrift

A 500 mL rb flask equipped with a magnetic stir bar and a temperature probe was charged with (E)-1-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)-2-(trifluoromethyl)benzamido)cyclopropanecarboxylic acid (9.2 g, 16.41 mmol), dichloromethane (DCM) (30 mL) and cooled in an ice water bath. With stirring, EDC HCl (3.15 g, 16.4 mmol) was added in one portion. After 5 min, the ice bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was diluted with DCM (100 mL), washed with brine (1×100 mL), dried over sodium sulfate and concentrated. The crude material was purified via an ISCO Rf medium pressure chromatography apparatus using a 330 g normal phase silica gel column and eluting with 0-30% EtOAc/hex gradient to afford the title compound (6.5 g, 73%): 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=8.1 Hz, 1H), 7.80 (dd, J=1.8, 0.8 Hz, 1H), 7.67 (dd, J=8.2, 1.8 Hz, 1H), 7.42 (s, 2H), 6.66 (d, J=15.9 Hz, 1H), 6.51 (dd, J=15.9, 7.8 Hz, 1H), 4.15 (p, J=8.7 Hz, 1H), 1.99-1.91 (m, 2H), 1.89-1.79 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −59.47, −68.51; ESIMS m/z 544.2 ([M+H]+).

Aufarbeitung

  1. customA 500 mL rb flask equipped with a magnetic stir bar
  2. temperaturecooled in an ice water bath
  3. customthe ice bath was removed
  4. stirringstirred for 2 h
  5. additionThe reaction mixture was diluted with DCM (100 mL)
  6. washwashed with brine (1×100 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude material was purified via an ISCO Rf medium pressure chromatography apparatus
  10. washeluting with 0-30% EtOAc/hex gradient

Quellen und Nachweise

ORD-Eintrag
ord-f4d8d138bed2413ba9ae48113e773185
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212164B2

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