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,4R)-4-(pyridin-3-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132962Notes

Reaction equation

HRID 132962 reaction equation
N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1C[C@H](OC2C=CC=CN=2)CN1C(C1C=CC=CC=1)C1C=CC=CC=1)O.[NH2:39][C@@H:40]([CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C@@H:41]([C@H:43]1[CH2:47][C@@H:46]([O:48][C:49]2[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=2)[CH2:45][N:44]1C(C1C=CC=CC=1)C1C=CC=CC=1)[OH:42].[C:77]([NH:80][C@:81]1([C@@H:130]([CH2:132][CH3:133])[CH3:131])[CH2:85][CH2:84][N:83]([C@@H:86]([CH2:121][CH2:122][C:123]2[CH:128]=[CH:127][CH:126]=[CH:125][CH:124]=2)[C:87](N[C@@H](CC2C=C(F)C=C(F)C=2)[C@@H]([C@H]2CCCCN2C(C2C=CC=CC=2)C2C=CC=CC=2)O)=[O:88])[C:82]1=[O:129])(=[O:79])[CH3:78].[Li+].[OH-]>CCO.O>[C:77]([NH:80][C@:81]1([C@@H:130]([CH2:132][CH3:133])[CH3:131])[CH2:85][CH2:84][N:83]([C@@H:86]([CH2:121][CH2:122][C:123]2[CH:124]=[CH:125][CH:126]=[CH:127][CH:128]=2)[C:87]([NH:39][C@@H:40]([CH2:68][C:69]2[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=2)[C@H:41]([OH:42])[C@H:43]2[CH2:47][C@@H:46]([O:48][C:49]3[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=3)[CH2:45][NH:44]2)=[O:88])[C:82]1=[O:129])(=[O:79])[CH3:78]

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 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 69195177(1S,2S)-2-amino-1-((2R,4R)-1-benzhydryl-4-(pyridin-3-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-olHCID 69195403(1S,2S)-2-amino-1-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)-3-(3,5-difluorophenyl)propan-1-ol

Product 1

HCID 69195175(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

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

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:

Workup

  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

Sources & evidence

ORD record
ord-cb646a1aa50e47b0ab58cd40faf4bd71
Source dataset
uspto-grants-2008_06
Patent number
US07388007B2

Reaction notes

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