Reaktion #220144

Reaktionsgleichung

(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)oxazolidin-2-one

(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-phenylbutanamide

LiOH

( B )

(1S,2S)-2-amino-1-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

(1S,2S)-2-amino-1-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

→

title compound

(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-3-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

Lösungsmittel

EtOH

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 4 h
2. 2
   Einengenthe mixture was concentrated
3. 3
   Sonstigeto remove EtOH and H2O
4. 4
   workup.ADDITIONwas added
5. 5
   ExtraktionThe mixture was extracted with ethyl acetate
6. 6
   Waschenthe organic phase was washed with sat. aqueous NaCl
7. 7
   Trocknendried (MgSO4)
8. 8
   Einengenconcentrated in vacuo

Vorschrift

Step 13 (B): (1S,2S)-2-amino-1-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)oxazolidin-2-one (Step 13 (A), 119 mg, 0.22 mmol) in EtOH (10 mL) was added a solution of LiOH (106 mg, 4.4 mmol) in H2O (3 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 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. Flash chromatography (silica gel, 0-10% MeOH/chloroform) gave 25.9 mg of the title compound as an opaque oil:

Quelle