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

HRID 1940653Notes

Reaction equation

HRID 1940653 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]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.N1C=CC=CC=1.[C:38](OC(=O)C)(=[O:40])[CH3:39].CO.C(Cl)(Cl)Cl>CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N:22]2[CH2:26][CH: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[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]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 21462594N-[[3-[3,5-difluoro-4-[4-(tert-butoxycarbonyl)-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 3 hours, the reaction was determined to be complete by TLC (20% MeOH/CHCl3, UV short wave). At this point, pyridine (8.26 mL, 102 mmol) was added, followed by treatment with acetic anhydride (9.64 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 19.167 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. filtrationThe reaction mixture was filtered through celite (the filter cake
  5. washwas washed with 500 mL EtOAc), the filtrate
  6. concentrationconcentrated down to approximately 600 mL
  7. washwashed with H2O (2×500 mL) and brine (500 mL)
  8. extractionThe aqueous portions were back-extracted with more EtOAc (2×500 mL)
  9. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a yellow solid
  13. customRecrystallization of the crude product from hot CHCl3 and hexane

Sources & evidence

ORD record
ord-8c0da42976e14b8baff9f710cd2e4935
Source dataset
uspto-grants-1997_12
Patent number
US05700799

Reaction notes

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