4-Methylmorpholine → Methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoate

HRID 1024430

Reaktionsgleichung

Reaktionsgleichung von HRID 1024430
CN1CCOCC1.[N+:8]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[S:21][C:20]([C:22]([O:24]CC)=O)=[N:19][CH:18]=2)=[CH:13][CH:12]=1)([O-:10])=[O:9].ClC(OCC(C)C)=O.Cl.[CH3:36][O:37][C:38](=[O:44])[C@H:39]([CH:41]([CH3:43])[CH3:42])[NH2:40]>C1COCC1.CCN(CC)CC>[CH3:42][CH:41]([CH3:43])[CH:39]([NH:40][C:22]([C:20]1[S:21][C:17]([C:14]2[CH:13]=[CH:12][C:11]([N+:8]([O-:10])=[O:9])=[CH:16][CH:15]=2)=[CH:18][N:19]=1)=[O:24])[C:38]([O:37][CH3:36])=[O:44]

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 111190Methyl valinate hydrochlorideHCID 53404682Ethyl 5-(4-nitrophenyl)thiazole-2-carboxylate2×

Produkt 1

HCID 67150324Methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoateAusbeute 74,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

N-methyl morpholine (1.01 ml) was added to a solution of 5-(4-nitrophenyl)thiazole-2-carboxylic acid (Intermediate 2, step B, 2.3 g) in THF (72 ml). The reaction mixture was stirred for 10 minutes at RT, cooled to −20° C. Isobutyl chloroformate (1.19 ml) was added and the mixture was stirred for 15-20 minutes at −20 to −30° C. This was followed by the addition of L-valine methyl ester hydrochloride (2.15 g) previously neutralized with Et3N (1.8 ml). The reaction mixture was stirred at −20 to −30° C. for 5 minutes and was then allowed to gradually warm to RT. The solvent was removed under reduced pressure and the crude material was chromatographed on silica gel in 15:85 EtOAc:CHCl3 to get pale yellow colored solid which was crystallized in EtOAc/Pet ether to yield 2.25 g (67%) of the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 8.95 (d, 1H), 8.7 (s, 1H), 8.34 (d, 2H), 8.09 (d, 2H), 4.33 (m, 1H), 3.68 (s, 3H), 2.27 (m, 1H), 0.95 (t, 6H); MS (ES+): m/z 364 (M+1).

Aufarbeitung

  1. temperaturecooled to −20° C
  2. stirringthe mixture was stirred for 15-20 minutes at −20 to −30° C
  3. stirringThe reaction mixture was stirred at −20 to −30° C. for 5 minutes
  4. temperatureto gradually warm to RT
  5. customThe solvent was removed under reduced pressure
  6. customthe crude material was chromatographed on silica gel in 15:85 EtOAc
  7. customCHCl3 to get pale yellow colored solid which
  8. customwas crystallized in EtOAc/Pet ether

Quellen und Nachweise

ORD-Eintrag
ord-5eb77b1a090848bd992832277debbd67
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722901B2

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