1,2-Dichloroethane → HCID 9892498, Verbindung

HRID 2215970Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2215970
C([O:8][C:9](=O)[NH:10][CH:11]([C:16]([N:18]1[CH2:22][CH2:21][CH2:20][CH:19]1[C:23](=[O:34])[NH:24][CH:25]1[CH2:29][C:28](=[O:30])[O:27][CH:26]1[O:31][CH2:32][CH3:33])=[O:17])[C:12]([CH3:15])([CH3:14])[CH3:13])C1C=CC=CC=1.[H][H].[NH2:38][C:39]1[CH:47]=[CH:46][C:42](C(O)=O)=[CH:41][C:40]=1[Cl:48].C(Cl)CCl.C(N(C(C)C)CC)(C)C>C(O)C.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[CH2:32]([O:31][CH:26]1[CH:25]([NH:24][C:23]([CH:19]2[CH2:20][CH2:21][CH2:22][N:18]2[C:16](=[O:17])[CH:11]([NH:10][C:9](=[O:8])[C:42]2[CH:46]=[CH:47][C:39]([NH2:38])=[C:40]([Cl:48])[CH:41]=2)[C:12]([CH3:13])([CH3:15])[CH3:14])=[O:34])[CH2:29][C:28](=[O:30])[O:27]1)[CH3:33]

Komponenten

9

Edukt 5

HCID 111,2-DichloroethaneHCID 172114-Amino-3-chlorobenzoic acidHCID 81531DiisopropylethylamineHCID 59730815Benzyl (S)-1-((S)-2-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-ylcarbamoyl)-pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamateHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 9892498HCID 9892498, VerbindungAusbeute 65,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9942167Palladium hydroxideKatalysatorHCID 702EthanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of {1-[2-(2-ethoxy-5-oxo-tetrahydrofuran-3-yl carbamoyl)-pyrrolidine-1-carbonyl]-2,2-dimethylpropyl}carbamic acid benzyl ester (0.12 g, 0.24 mmol) in ethanol (5 mL) was treated with 10% palladium hydroxide on carbon (0.05 g), was stirred under 1 atm hydrogen pressure for 4 h, was filtered through Celite and was evaporated. The crude intermediate was dissolved in dichloromethane (5 mL), and was treated with 4-amino-3-chlorobenzoic acid (0.04 g, 0.26 mmol), EDC (0.06 g, 0.29 mmol) and diisopropylethylamine (0.13 mL, 0.71 mmol) and was stirred at room temperature under nitrogen for 20 h. The reaction was diluted with ethyl acetate, was washed with 10% potassium bisulfate, saturated sodium bicarbonate and brine, was dried (sodium sulfate) and was evaporated. Purification by flash chromatography (SiO2) eluted with 7:3 ethyl acetate hexanes provided 1-[2-(4-amino-3-chlorobenzoylamino)-3,3-dimethylbutyryl]pyrrolidine-2-carboxylic acid (2-ethoxy-5-oxo-tetrahydrofuran-3-yl)amide (0.08 g, 62% yield) as a colorless film. 1H-NMR (500 MHz, CDCl3) d 7.67 (d, J=2.0 Hz, 1H), 7.50 (m, 0.2H), 7.44 (dd, J=8.4, 2.0 Hz, 1.0H), 7.33 (d, J=8.0 Hz, 0.8H), 6.69 (d, J=8.4 Hz, 1H), 6.55 (d, J=9.2 Hz, 1H), 5.39 (d, J=5.2 Hz, 0.8H), 5.29 (s, 0.2H), 4.79 (d, J=9.4 Hz, 1H), 4.62 (m, 0.8H), 4.50 (m, 1.0H), 4.25 (m, 0.2H), 3.83 (m, 0.8H), 3.77 (m, 0.2H), 3.62 (m, 0.8H), 3.55 (m, 0.2H), 2.92 (m, 0.2H), 2.76 (dd, J=17.2, 8.4 Hz, 0.8H), 2.30 (m, 2H), 2.05 (m, 1H), 1.93 (m, 1.0H), 1.85 (m, 1H), 1.22 (t, J=7.1 Hz, 2.4H), 1.16 (t, J=7.1 Hz, 0.6H), 1.00 (s, 9H) ppm. 1H-NMR shows ˜8:2 syn:anti epimers. LC/MS (ES+): m/e=509.08 (M+H).

Aufarbeitung

  1. filtrationwas filtered through Celite
  2. customwas evaporated
  3. dissolutionThe crude intermediate was dissolved in dichloromethane (5 mL)
  4. washwas washed with 10% potassium bisulfate, saturated sodium bicarbonate and brine
  5. dry with materialwas dried (sodium sulfate)
  6. customwas evaporated
  7. customPurification by flash chromatography (SiO2)
  8. washeluted with 7:3 ethyl acetate hexanes

Quellen und Nachweise

ORD-Eintrag
ord-7adf68368a30426aa0c7c24bbe8edf4f
Quelldatensatz
uspto-grants-2006_09
Patentnummer
US07109357B2

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