1,3-Diethyl 2-oxopropanedioate → (1S)-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-1-isopropyl-4-oxocyclopent-2-ene-1-carboxamide

HRID 643529Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 643529
N[CH:2]1[CH2:6][C@@:5]([CH:26]([CH3:28])[CH3:27])([C:7]([NH:9][CH2:10][C:11]2[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=2[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:8])[CH:4]=[CH:3]1.[O:29]=C(C(OCC)=O)C(OCC)=O.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[C:22]([O:21][C:12]1[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[CH:16][C:11]=1[CH2:10][NH:9][C:7]([C@:5]1([CH:26]([CH3:28])[CH3:27])[CH2:6][C:2](=[O:29])[CH:3]=[CH:4]1)=[O:8])([CH3:25])([CH3:24])[CH3:23]

Komponenten

5

Edukt 3

HCID 691051,3-Diethyl 2-oxopropanedioateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58617203(1S)-4-amino-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]1-isopropylcyclopent-2-ene-1-carboxamide

Produkt 1

HCID 58617127(1S)-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-1-isopropyl-4-oxocyclopent-2-ene-1-carboxamideAusbeute 91,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of (1S)-4-amino-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]1-isopropylcyclopent-2-ene-1-carboxamide (35 g, 88 mmol) and diethyl oxomalonate (31 g, 176 mmol) in toluene (350 mL) was refluxed until no more starting material left as judged by HPLC. The reaction mixture was cooled to 0° C. and 1,8-diazabicyclo[5.4.0]undec-7-ene (27 g, 176 mmol) was added. The reaction mixture was then warmed to r.t. and stirred at this temperature for 1 hr before being quenched with 1M HCl and vigorously stirred for 1 hr. The reaction mixture was diluted with EtOAc and the two layers were separated. The aqueous phase was then extracted with EtOAc (5×). The organics were combined, dried over sodium sulfate and evaporated to dryness. The crude was purified by column chromatography on silica gel eluting with hexane:EtOAc (11:1) to yield 32 g of (1S)—N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-1-isopropyl-4-oxocyclopent-2-ene-1-carboxamide as a pale yellow solid.

Aufarbeitung

  1. temperaturewas refluxed until
  2. waitleft
  3. temperatureThe reaction mixture was then warmed to r.t.
  4. custombefore being quenched with 1M HCl
  5. stirringvigorously stirred for 1 hr
  6. additionThe reaction mixture was diluted with EtOAc
  7. customthe two layers were separated
  8. extractionThe aqueous phase was then extracted with EtOAc (5×)
  9. dry with materialdried over sodium sulfate
  10. customevaporated to dryness
  11. customThe crude was purified by column chromatography on silica gel eluting with hexane:EtOAc (11:1)

Quellen und Nachweise

ORD-Eintrag
ord-2b00d085bee44daf85e4f90228af435b
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07700591B2

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