Pyridine → (S)-N-[[3-[3,5-difluoro-4-[4-[2-(1-piperidinyl)ethyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1078525Notes

Reaction equation

HRID 1078525 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:22]2[CH2:26][CH:25]([CH2:27][N:28]=[N+]=[N-])[O:24][C:23]2=[O:31])[CH:5]=[C:6]([F:21])[C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]1.[N:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[C:38](OC(=O)C)(=[O:40])[CH3:39].CO.[CH:47](Cl)(Cl)Cl>CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:22]2[CH2:26][C@H:25]([CH2:27][NH:28][C:38](=[O:40])[CH3:39])[O:24][C:23]2=[O:31])[CH:5]=[C:6]([F:21])[C:7]=1[N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:47][N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 21584188Chloroform methanolHCID 54095168[[3-[3,5-Difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]azide

Product 1

HCID 54560046(S)-N-[[3-[3,5-difluoro-4-[4-[2-(1-piperidinyl)ethyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideYield 83%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The [[3-[3,5-difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]azide (22.4 g, 51 mmol) was dissolved in 1 L of EtOAc and then degassed three times with N2. Next, 10% Pd-C (4.48 g, 20% by weight) was added and the solution was degassed again three times (with N2) before replacing the atmosphere with H2 (balloon). After hours, the reaction was determined to be complete by TLC (20% MeOH/CHCl3, UV short wave). At this point, pyridine (8.25 mL, 102 mmol) was added, followed by treatment with acetic anhydride (9.54 mL, 102 mmol). The reaction mixture was allowed to stir overnight at room temperature. The reaction was found to be complete by TLC (20% MeOH/CHCl3, UV short wave). The reaction mixture was filtered through celite (the filter cake was washed with 500 mL EtOAc), the filtrate concentrated down to approximately 600 mL, and washed with H2O (2×500 mL) and brine (500 mL). The aqueous portions were back-extracted with more EtOAc (2×500 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to give a yellow solid. Recrystallization of the crude product from hot CHCl3 and hexane afforded 19.157 g (83%) of the title compound as a white solid with mp 177°-179° C.

Workup

  1. customdegassed three times with N2
  2. additionNext, 10% Pd-C (4.48 g, 20% by weight) was added
  3. customthe solution was degassed again three times (with N2)
  4. waitAfter hours
  5. filtrationThe reaction mixture was filtered through celite (the filter cake
  6. washwas washed with 500 mL EtOAc), the filtrate
  7. concentrationconcentrated down to approximately 600 mL
  8. washwashed with H2O (2×500 mL) and brine (500 mL)
  9. extractionThe aqueous portions were back-extracted with more EtOAc (2×500 mL)
  10. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a yellow solid
  14. customRecrystallization of the crude product from hot CHCl3 and hexane

Sources & evidence

ORD record
ord-f9eb8f71d69c4352a12dc3d25c79d848
Source dataset
uspto-grants-1996_08
Patent number
US05547950

Reaction notes

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