Lithium Hydroxide → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4S)-4-hydroxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132966Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 132966
[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=2)[C@@H:15]([C@H:17]2[CH2:22][CH2:21][CH2:20]C[N:18]2C(C2C=CC=CC=2)C2C=CC=CC=2)[OH:16])=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2].N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@@H]1N(C(C2C=CC=CC=2)C2C=CC=CC=2)C[C@@H](O)C1)[OH:61].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.[Li+].[OH-]>CCO.O>[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:38]=[C:39]([F:44])[CH:40]=[C:41]([F:43])[CH:42]=2)[C@H:15]([OH:16])[C@H:17]2[CH2:22][C@H:21]([OH:61])[CH2:20][NH:18]2)=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 3939Lithium HydroxideHCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69194452(3S,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol

Produkt 1

HCID 69195085(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4S)-4-hydroxypyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamideAusbeute 84 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

Step 15 (A): (3S,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation K, 60 mg, 0.129 mmol) in EtOH (5 mL) was added a solution of LiOH (62 mg, 2.58 mmol) in H2O (1.25 mL). This reaction mixture was stirred at reflux for 4 h. After cooling down to rt, the mixture was concentrated to remove EtOH and H2O was added followed by 1N HCl (8 mL) solution and pH 7 buffer. The mixture was extracted with ethyl acetate and the organic phase was washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo to give the title compound (47.3 mg, 84% yield) as an opaque oil: 1H NMR (CDCl3, 300 MHz) δ 2.32-2.39 (1H, m), 2.49-2.62 (3H, m), 2.79-2.80 (1H, m), 3.18 (1H, d, J=12 Hz), 3.49-3.58 (2H, m), 4.28 (1H, t, J=6 Hz), 4.63 (1H, s), 5.55 (1H, s), 5.96 (4H, brd s), 6.62-6.68 (3H, m), 7.20-7.36 (6H, m), 7.77 (4H, d, J=6 Hz). HPLC retention time: 1.20 min (method A). MS (ESI) (M+H)+ 439.16.

Aufarbeitung

  1. temperatureat reflux for 4 h
  2. concentrationthe mixture was concentrated
  3. customto remove EtOH and H2O
  4. additionwas added
  5. extractionThe mixture was extracted with ethyl acetate
  6. washthe organic phase was washed with sat. aqueous NaCl
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bcf57ec2f7334e4f96f692e035e19d03
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388007B2

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