Dicyclohexylcarbodiimide → tert-butyl 2-methyl-2-[(Z)-[2-oxo-2-[[(3S)-2-oxoazetidin-3-yl]amino]-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxypropanoate

HRID 1166006Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1166006
C1(CO[C:9](=[O:16])[NH:10][C@H:11]2[CH2:14][NH:13][C:12]2=[O:15])C=CC=CC=1.[CH3:17][C:18]([CH3:57])([O:20][C:21](=[O:56])[C:22]([CH3:55])([CH3:54])[O:23]/[N:24]=[C:25](/[C:29]1[N:30]=[C:31]([NH:34][C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[S:32][CH:33]=1)\C(O)=O)[CH3:19].C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>[Pd].O.CN(C=O)C.CO>[CH3:19][C:18]([CH3:57])([O:20][C:21](=[O:56])[C:22]([CH3:55])([CH3:54])[O:23]/[N:24]=[C:25](/[C:29]1[N:30]=[C:31]([NH:34][C:35]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[S:32][CH:33]=1)\[C:9]([NH:10][C@H:11]1[CH2:14][NH:13][C:12]1=[O:15])=[O:16])[CH3:17]

Komponenten

10

Edukt 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 11039088(Z)-alpha-((2-(tert-Butoxy)-1,1-dimethyl-2-oxoethoxy)imino)-2-(tritylamino)thiazol-4-acetic acidHCID 12834624benzyl N-[(3S)-2-oxoazetidin-3-yl]carbamate

Produkt 1

HCID 88606817tert-butyl 2-methyl-2-[(Z)-[2-oxo-2-[[(3S)-2-oxoazetidin-3-yl]amino]-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxypropanoateAusbeute 59.396,898 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 2.20 g (0.01 mmol) of (S)-(2-oxo-3-azetidinyl) carbamic acid phenylmethyl ester, 125 mL of methanol, and 0.68 g of 10% palladium on carbon catalyst was hydrogenated (5 minutes) on a parr apparatus at an initial gauge pressure of 50 psi. After filtration of the catalyst, the solution was concentrated to dryness under reduced pressure. The residual (S)-3-amino-2-azetidinone was dissolved in 10 mL of DMF and added to a mixture of 5.71 g (0.01 mol) of (Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[(triphenylmethyl)amino]-4-thiazole acetic acid, 40 mL of DMF, 2.06 g (0.01 mol) of N,N'-dicyclo-hexylcarbodiimide and 1.35 g (0.01 mol) of 1-hydroxybenzo-triazole. The mixture was stirred for 4 hours, diluted with 500 mL of water and adjusted to pH 7.5 with aqueous NaHCO3. The mixture was extracted with four 300 mL portions of ethyl acetate. The combined extracts were washed with water and brine, dried (Na2SO4), decolorized with charcoal and concentrated to dryness. After purification by HPLC on a Waters Prep 500, using 4:1 ethyl acetate-hexane, 3.8 g of (S,Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-N-(2-oxo-3-azetidinyl)-2-[(triphenylmethyl)amino]-4-thiazoleacetamide was obtained.

Aufarbeitung

  1. custom(5 minutes)
  2. filtrationAfter filtration of the catalyst
  3. concentrationthe solution was concentrated to dryness under reduced pressure
  4. dissolutionThe residual (S)-3-amino-2-azetidinone was dissolved in 10 mL of DMF
  5. extractionThe mixture was extracted with four 300 mL portions of ethyl acetate
  6. washThe combined extracts were washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customAfter purification by HPLC on a Waters Prep 500

Quellen und Nachweise

ORD-Eintrag
ord-83a347fc052d494e98bbe60451204b32
Quelldatensatz
uspto-grants-1990_03
Patentnummer
US04912214

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