Cesium carbonate → tert-butyl (R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate

HRID 1183897Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1183897
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:3]=1.Br[CH2:16][C@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:18][C@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[CH3:16])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:3]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 57081792(R)-tert-butyl 1-bromopropan-2-ylcarbamateHCID 1355820244-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol

Produkt 1

HCID 86633179tert-butyl (R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamateAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 180AcetoneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol (500 mg, 2643 μmol), (R)-tert-butyl 1-bromopropan-2-ylcarbamate (755 mg, 3171 μmol) and cesium carbonate (1205 mg, 3700 μmol) were weighed into a vial with anhydrous acetone (3.0 mL). The reaction was heated in a microwave at 100° C. for an hour. After this time, the crude LC/MS showed that the reaction was nearly complete. Thus, the solvent was evaporated and the resulting material was extracted (3 mL each of H2O and CH2Cl2). The aqueous layer was extracted again with CH2Cl2 (3 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography (0, 20, 50, 70, 100% EtOAc/Hexanes) to yield tert-butyl(R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate (487 mg, 1.41 mmol, 50.7%) as a light brown colored oil. LCMS m/z 347.1 (M+H); 1H NMR (400 MHz, MeOH-d4) δ ppm 0.92 (d, J=6.57 Hz, 3 H), 1.32 (s, 9 H), 3.60 (s, 3 H), 3.69-3.76 (m, 1 H), 3.79-3.94 (m, 2 H), 6.13 (d, J=1.77 Hz, 1 H), 6.57 (d, J=2.78 Hz, 1 H), 6.72 (dd, J=8.59, 2.78 Hz, 1 H), 6.83 (d, J=8.84 Hz, 1 H), 7.36 (d, J=2.02 Hz, 1 H).

Aufarbeitung

  1. customThus, the solvent was evaporated
  2. extractionthe resulting material was extracted (3 mL each of H2O and CH2Cl2)
  3. extractionThe aqueous layer was extracted again with CH2Cl2 (3 mL)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by column chromatography (0, 20, 50, 70, 100% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-a403b5403fec4eb29b3a627b7f252f87
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08664258B2

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