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

HRID 1014862Notes

Reaction equation

HRID 1014862 reaction equation
FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H](OCC=C)CN2)OC(=O)N1.N[C@@H](CC1C=C(F)C=C(F)C=1)[C@@H]([C@H]1COCCN1C(C1C=CC=CC=1)C1C=CC=CC=1)O.[F:57][C:58]1[CH:59]=[C:60]([CH:87]=[C:88]([F:90])[CH:89]=1)[CH2:61][C@H:62]1[C@@H:66]([C@H:67]2[CH2:72][O:71][CH2:70][CH2:69][N:68]2[CH:73]([C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)[C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[O:65][C:64](=[O:86])[NH:63]1.[Li+].[OH-]>CCO.O>[F:57][C:58]1[CH:59]=[C:60]([CH:87]=[C:88]([F:90])[CH:89]=1)[CH2:61][C@H:62]1[C@@H:66]([C@H:67]2[CH2:72][C@H:70]([OH:71])[CH2:69][N:68]2[CH:73]([C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][CH:81]=2)[O:65][C:64](=[O:86])[NH:63]1

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 59733914(1S,2S)-2-Amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-olHCID 67315700(4S,5S)-4-(3,5-Difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-oneHCID 67316146(4S,5R)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)pyrrolidin-2-yl)oxazolidin-2-one

Product 1

HCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneYield 95.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Step D (8): (1S,2S)-2-Amino-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol. To a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((R)-4-benzhydrylmorpholin-3-yl)oxazolidin-2-one (step D (7), 85 mg, 0.18 mmol) in EtOH (2 mL) was added a solution of LiOH (66 mg, 2.75 mmol) in H2O (1 mL). This reaction mixture was brought to 98° C. and stirred for overnight. Solvent was removed and 1N HCl solution (50 mL) was added to the mixture and washed with diethyl ether. The aqueous phase was basified with 50% aqueous NaOH solution. This mixture was extracted with ethyl acetate. The combined organic layer was dried (Na2SO4), and concentrated in vacuo to give 80 mg of the title compound: 1H NMR (CDCl3, 500 MHz) δ 1.94-2.06 (3H, m), 2.30 (1H, dd, J=10, 15 Hz), 2.51-2.59 (1H, m), 2.73-2.81 (1H, m), 2.90 (1H, m), 2.95 (1H, m), 3.08 (1H, m), 3.70 (1H, m), 3.80 (1H, dt, J=5, 10 Hz), 3.91 (1H, m), 4.09 (1H, m), 4.14 (1H, m), 5.05 (1H, s), 6.60-6.68 (3H, m), 7.15-7.31 (6H, m), 7.37 (2H, d, J=10 Hz), 7.42 (2H, d, J=5 Hz). MS (ESI) (M+H)+ 439.20.

Workup

  1. customwas brought to 98° C.
  2. customSolvent was removed
  3. addition1N HCl solution (50 mL) was added to the mixture
  4. washwashed with diethyl ether
  5. extractionThis mixture was extracted with ethyl acetate
  6. dry with materialThe combined organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-de3ca0b983b0488fb8c87971eb917647
Source dataset
uspto-grants-2011_07
Patent number
US07981913B2

Reaction notes

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