Diisopropylethylamine → (2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylate

HRID 20934

Reaktionsgleichung

Reaktionsgleichung von HRID 20934
[F:1][C:2]1[CH:3]=[C:4]([CH:40]=[C:41]([F:43])[CH:42]=1)[CH2:5][C@H:6]([C:25]([N:27]1[C@@H:31]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:30][O:29][C:28]1=[O:39])=[O:26])[C@@H:7]([CH:9]1[CH2:13][CH:12]([O:14][CH2:15][CH:16]=[CH2:17])[CH2:11][N:10]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[OH:8].C([C@H]1COC(=O)N1C(=O)CCC1C=C(F)C=C(F)C=1)C1C=CC=CC=1.B(OS(C(F)(F)F)(=O)=O)(CCCC)CCCC.CCN(C(C)C)C(C)C.C(O[C@H]1CN(C(OC(C)(C)C)=O)[C@@H](C=O)C1)C=C>C(Cl)Cl>[F:43][C:41]1[CH:40]=[C:4]([CH:3]=[C:2]([F:1])[CH:42]=1)[CH2:5][C@H:6]([C:25]([N:27]1[C@@H:31]([CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:30][O:29][C:28]1=[O:39])=[O:26])[C@@H:7]([C@H:9]1[CH2:13][C@@H:12]([O:14][CH2:15][CH:16]=[CH2:17])[CH2:11][N:10]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[OH:8]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 2724243Methanesulfonic acid, 1,1,1-trifluoro-, anhydride with B,B-dibutylborinic acidHCID 59733915(S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-oneHCID 67316356tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylateHCID 86608470(2R,4R)-tert-butyl 4-(allyloxy)-2-formylpyrrolidine-1-carboxylate

Produkt 1

HCID 67316359(2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylateAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Step A (5): 2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylate. To a solution of (S)-4-benzyl-3-(3-(3,5-difluorophenyl)propanoyl)oxazolidin-2-one (Preparation B, 1.47 g, 4.27 mmol) in CH2Cl2 (15 ml) at −78° C. was added Bu2BOTf (5.12 ml, 5.12 mmol, 1M in CH2Cl2) and Hunig's base (1.12 ml, 6.41 mmol). The resulting mixture was brought to 0° C. and stirred for 30 min. The mixture was again cooled to −78° C. and a solution of (2R,4R)-tert-butyl 4-(allyloxy)-2-formylpyrrolidine-1-carboxylate (Step A (4), 1.09 g, 4.27 mmol) in CH2Cl2 (10 ml) was added dropwise. When the addition was complete, the mixture was stirred at −78° C. for 5 min., then was allowed to warm to rt. After stirring at rt for 4 h. the mixture was concentrated in vacuo. Flash chromatography (silica gel, 0-75% ethyl acetate/hexane) gave 1.22 g (48%) of (2R,4R)-tert-butyl 2-((1S,2S)-2-(3,5-difluorobenzyl)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-hydroxy-3-oxopropyl)-4-(allyloxy)pyrrolidine-1-carboxylate as a slightly yellow oil: 1H NMR (CDCl3, 300 MHz) δ 1.49 (9H, s), 2.03-2.22 (2H, m), 2.31 (1H, d, J=12 Hz), 2.98 (1H, dd, J=3, 15 Hz), 3.07 (1H, t, J=12 Hz), 3.42-3.57 (3H, m), 3.97-4.11 (8H, m), 4.57 (2H, brd s), 5.17-5.30 (2H, m), 5.81-5.94 (1H, m), 6.61 (1H, t, J=9 Hz), 6.90 (2H, brd s), 7.00 (2H, brd s), 7.26 (3H, m). HPLC retention time: 2.04 min (method A). MS (ESI) (M+H)+ 601.37.

Aufarbeitung

  1. customwas brought to 0° C.
  2. additionWhen the addition
  3. stirringthe mixture was stirred at −78° C. for 5 min.
  4. temperatureto warm to rt
  5. stirringAfter stirring at rt for 4 h. the mixture
  6. concentrationwas concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9d0225a190ec4ebeb569bf324156df4c
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07745470B2

Verknüpfte Notizen

Wird geladen…