Ammonium Chloride → HCID 178471785, Verbindung

HRID 505300Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 505300
CC(C)([O-])C.[K+].[F:7][C:8]([F:27])([F:26])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[NH:21][C@H:20]2[CH3:25])[CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1.Cl[CH2:29][C:30]1[C:35]([N:36]([CH2:39][C@H:40]2[CH2:45][CH2:44][C@H:43]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:42][CH2:41]2)[CH2:37][CH3:38])=[CH:34][CH:33]=[CH:32][N:31]=1.[NH4+].[Cl-]>CN(C=O)C.O>[F:27][C:8]([F:7])([F:26])[C:9]1[CH:10]=[C:11]([C@H:19]2[O:23][C:22](=[O:24])[N:21]([CH2:29][C:30]3[C:35]([N:36]([CH2:39][C@H:40]4[CH2:45][CH2:44][C@H:43]([CH2:46][C:47]([O:49][CH2:50][CH3:51])=[O:48])[CH2:42][CH2:41]4)[CH2:37][CH3:38])=[CH:34][CH:33]=[CH:32][N:31]=3)[C@H:20]2[CH3:25])[CH:12]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=1

Komponenten

7

Edukt 4

HCID 25517Ammonium ChlorideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-oneHCID 23665647Potassium tert-butoxideHCID 178471784HCID 178471784, Verbindung

Produkt 1

HCID 178471785HCID 178471785, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

Potassium t-butoxide (55.3 mg, 0.493 mmol) was added to a stirred solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (180.2 mg, 0.575 mmol) in dry DMF (5 mL) at room temperature under N2. The solution was stirred for 5 min at room temperature. A solution of ethyl (trans-4-{[[2-(chloromethyl)pyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate (145.0 mg, 0.411 mmol) in dry DMF (2 mL) was added via cannula and the reaction was stirred at room temperature for 3 h. Saturated aqueous NH4Cl (5 mL) and water (5 mL) were added and the mixture was extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate. Rf=0.77 (50% EtOAc/hexanes). LCMS calc.=630.3; found=630.3 (M+1)+. 1H NMR (600 MHz, CDCl3): i 8.31 (dd, J=1.3, 4.6 Hz, 1 H); 7.85 (s, 1 H); 7.80 (s, 2 H); 7.43 (dd, J=1.3, 8.1 Hz, 1 H); 7.17 (dd, J=4.7, 8.1 Hz, 1 H); 5.78 (d, J=8.5 Hz, 1 H); 4.91 (d, J=16.7 Hz, 1 H); 4.45 (d, J=16-7 Hz, 1 H); 4.36-4.30 (m, 1 H); 4.06 (q, J=7.1 Hz, 2 H); 2.96-2.90 (m, 2 H); 2.82-2.74 (m, 2 H); 2.11 (d, J=6.8 Hz, 2 H); 1.80-1.75 (m, 2 H); 1.73-1.67 (m, 3 H); 1.30 (m, 1 H); 1.20 (t, J=7.1 Hz, 3 H); 0.96 (t, J=7.0 Hz, 3H); 0.93-0.77 (m, 4 H); 0.66 (d, J=6.7 Hz, 3 H).

Aufarbeitung

  1. stirringthe reaction was stirred at room temperature for 3 h
  2. extractionthe mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThis was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-da509c78ab784733a30bea04a1159b0f
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781426B2

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