Tributylphosphine → 3-{4-[3-(2-Chloro-3,6-difluorophenoxy)propyl]phenyl}-2-cyano-n-cyclopropyl-n-(2,3-dichlorobenzyl)-2-methylpropanamide

HRID 561851Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 561851
[C:1]([C:3]([CH3:30])([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][OH:29])=[CH:22][CH:21]=1)[C:4]([N:6]([CH:16]1[CH2:18][CH2:17]1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[Cl:15])=[O:5])#[N:2].[Cl:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1O.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>CCOCC.C1(C)C=CC=CC=1>[Cl:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1[O:29][CH2:28][CH2:27][CH2:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:3]([C:1]#[N:2])([CH3:30])[C:4]([N:6]([CH:16]2[CH2:18][CH2:17]2)[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=2[Cl:15])=[O:5])=[CH:25][CH:24]=1

Komponenten

7

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27735612-Chloro-3,6-difluorophenolHCID 667613132-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-3-[4-(3-hydroxypropyl)phenyl]-2-methylpropanamide

Produkt 1

HCID 667621493-{4-[3-(2-Chloro-3,6-difluorophenoxy)propyl]phenyl}-2-cyano-n-cyclopropyl-n-(2,3-dichlorobenzyl)-2-methylpropanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

2-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-3-[4-(3-hydroxypropyl)phenyl]-2-methylpropanamide from the previous step (1 eq.) and 2-chloro-3,6-difluorphenol (4 eq.) were taken up in freshly deoxygenated toluene (0.05 M). To this solution was then added 1,1′-(azodicarbonyl)-dipiperidine (4 eq.) and finally tributylphosphine (4 eq.). The resulting yellow solution was heated at 80° C. for 3 h. The reaction mixture was cooled to RT, diluted with ether, and washed with 1 N aq. NaOH. The aqueous wash was back extracted with ether and the combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a yellow semi-solid. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with 1 N aq. NaOH
  3. washThe aqueous wash
  4. extractionwas back extracted with ether
  5. dry with materialthe combined organic extracts were dried over MgSO4
  6. filtrationFiltration and concentration of the filtrate in vacuo
  7. customafforded a yellow semi-solid
  8. customPurification of the crude product
  9. customthus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-0b3fc09fc9d2416bae35af9a699fd9d7
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063105B2

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