Potassium Carbonate → (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one

HRID 20938

Reaktionsgleichung

Reaktionsgleichung von HRID 20938
FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](OCC=C)CN2C(OC(C)(C)C)=O)OC(=O)N1.[F:32][C:33]1[CH:34]=[C:35]([CH:62]=[C:63]([F:65])[CH:64]=1)[CH2:36][C@H:37]1[C@@H:41]([C@H:42]2[CH2:47][O:46][CH2:45][CH2:44][N:43]2[CH:48]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[O:40][C:39](=[O:61])[NH:38]1.FC1C=C(C=C(F)C=1)C[C@@H]([C@@H]([C@H]1C[C@@H](OCC=C)CN1C(OC(C)(C)C)=O)O)C(O)=O.C(=O)([O-])[O-].[K+].[K+].BrC(C1C=CC=CC=1)C1C=CC=CC=1>C(#N)C>[F:32][C:33]1[CH:34]=[C:35]([CH:62]=[C:63]([F:65])[CH:64]=1)[CH2:36][C@H:37]1[C@@H:41]([C@H:42]2[CH2:47][C@H:45]([OH:46])[CH2:44][N:43]2[CH:48]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[O:40][C:39](=[O:61])[NH:38]1

Komponenten

7

Edukt 5

HCID 11430Potassium CarbonateHCID 236603BromodiphenylmethaneHCID 67315700(4S,5S)-4-(3,5-Difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-oneHCID 67315782(2R,4R)-tert-butyl 2-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-4-(allyloxy)pyrrolidine-1-carboxylateHCID 67316915(2S,3S)-2-(3,5-difluorobenzyl)-3-((2R,4R)-4-(allyloxy)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-3-hydroxypropanoic acid

Produkt 1

HCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

Step D (7): (4S,5S)-4-(3,5-Difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-one. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-(morpholin-3-yl)oxazolidin-2-one (step D (6), 180 mg, 0.6 mmol) in acetonitrile (5 mL) were added potassium carbonate (248 mg, 1.8 mmol) and bromodiphenylmethane (296 mg, 1.2 mmol). This mixture was stirred at 100° C. for 1.5 h. Solvent was removed and the crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 65% EtOAc/Hexane step gradient) to give 85 mg of the title compound (29% yield): 1H NMR (CDCl3, 500 MHz) δ 2.14 (1H, m), 2.76 (2H, d, J=15 Hz), 2.98 (1H, d, J=5 Hz), 3.15 (1H, m), 3.52 (1H, m), 3.67 (1H, m), 3.87-3.94 (3H, m), 5.23 (2H, d, J=10 Hz), 5.31 (1H, m), 6.56 (2H, d, J=5 Hz), 6.70 (1H, m), 7.16 (1H, d, J=5 Hz), 7.21-7.37 (7H, m), 7.41 (2H, d, J=10 Hz). MS (ESI) (M+H)+ 465.14.

Aufarbeitung

  1. customSolvent was removed
  2. customthe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 65% EtOAc/Hexane step gradient)

Quellen und Nachweise

ORD-Eintrag
ord-06f85538836f415eb143db47b19435fb
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

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