Ethyl Acetate → HCID 178502377, Verbindung

HRID 1776014Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776014
[CH3:1][O:2][C:3](=[O:28])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].CC1(C)C(C)(C)OB([C:37]2[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:28])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:37]3[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 178502354HCID 178502354, Verbindung

Produkt 1

HCID 178502377HCID 178502377, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Versuchsvorschrift

To a solution of ((S)-1-{(S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (9.10 g, 20.34 mmol) in dioxane:water (3:1) (200 mL), was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (4.9 g, 22.37 mmol), sodium carbonate (4.3 g, 40.68 mmol) and Pd(dppf)2Cl2 (0.83 g, 5%). The reaction mixture was warmed to reflux under nitrogen, stirred for 4 h, cooled to RT, filtered, and concentrated. The residue was extracted with ethyl acetate and water, dried with sodium sulfate and concentrated. The crude product was purified by silica gel chromatography eluting with 1:1 hexane:ethyl acetate, to provide the title compound (7 g, 75% yield) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ (ppm) 7.62-7.55 (m, 1H), 7.50 (d, J=8.0 Hz, 2H), 7.40 (m, 3H), 7.18 (s, 1H), 6.75 (d, J=8.4 Hz, 2H), 5.50 (d, J=9.2 Hz, 1H), 5.25-5.23 (m, 1H), 4.31 (t, J=2.4 Hz, 1H), 3.83-3.80 (m, 1H), 3.67 (s, 3H), 3.59-3.53 (m, 1H), 3.05-2.95 (m, 1H), 2.40-2.30 (m, 1H), 2.19-2.11 (m, 1H), 2.08-2.03 (m, 1H), 1.98-1.93 (m, 1H), 1.07-1.01 (m, 1H), 0.85 (d, J=6.8 Hz, 6H).

Aufarbeitung

  1. temperatureThe reaction mixture was warmed
  2. temperatureto reflux under nitrogen
  3. filtrationfiltered
  4. concentrationconcentrated
  5. extractionThe residue was extracted with ethyl acetate and water
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 1:1 hexane

Quellen und Nachweise

ORD-Eintrag
ord-5b7877f70d3c430da0ee9e65742975f7
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260414B2

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