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

HRID 132941Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 132941
[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:15][C@@H:14]([O:16]CC=C)[CH2:13][N:12]2[CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C:8](=[O:33])[NH:7]1.C(O[C@H]1C[C@H]([C@H]2OC(=O)N[C@H]2CC2C=C(F)C=C(F)C=2)N(C(C2C=CC=CC=2)C2C=CC=CC=2)C1)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](O)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.C(O)(=O)C>C1COCC1.C(OCC)(=O)C.CCCCCC>[F:37][C:35]1[CH:34]=[C:4]([CH:3]=[C:2]([F:1])[CH:36]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][N:12]2[CH:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:33])[NH:7]1

Komponenten

9

Edukt 6

HCID 176Acetic AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 58608196(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 67316078(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)oxazolidin-2-oneHCID 69195358(3S,5R)-5-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-1-benzhydrylpyrrolidin-3-yl acetate

Produkt 1

HCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 21226206Ethyl acetate hexaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Step K (1): (3S,5R)-5-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-1-benzhydrylpyrrolidin-3-yl acetate. To a solution of triphenylphosphine (510 mg, 1.94 mmol) in THF (20 mL) at 0° C. was added DEAD (0.36 mL, 1.94 mmol) and the mixture was allowed to come to rt for 5 min and was again cooled to 0° C. A solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 750 mg, 1.62 mmol) in THF (20 mL) was added and the mixture was allowed to come to rt for 5 min and was again cooled to 0° C. Acetic acid (0.093 mL, 1.62 mmol) was added and the mixture was warmed to rt and stirred for 30 min. pH 7 buffer was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 5-100% ethyl acetate/hexane) gave 661 mg (81% yield) of the title compound as a clear, very slightly yellow oil: 1H NMR (CDCl3, 500 MHz) δ 1.31-1.34 (1H, m), 2.08-2.16 (1H, m), 2.39 (3H, m), 2.80 (1H, brd s), 3.26 (1H, brd s), 3.60 (2H, brd s), 4.11 (1H, m), 4.27-4.33 (1H, m), 4.91 (2H, m), 5.28 (1H, m), 6.40 (2H, brd s), 6.51 (2H, m), 6.69 (1H, m), 7.22 (1H, m), 7.28-7.49 (8H, m). HPLC retention time: 1.50 min (method A). MS (ESI) (M+H)+ 507.17.

Aufarbeitung

  1. waitto come to rt for 5 min
  2. temperaturewas again cooled to 0° C
  3. temperaturethe mixture was warmed to rt
  4. additionbuffer was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe combined organic phases were washed with sat. aqueous NaCl
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-51d3ae56f3b642b2b25b14ab78aabaf6
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388007B2

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