Nitrogen → HCID 70197353, compound

HRID 1418662Notes

Reaction equation

HRID 1418662 reaction equation
[Si:1]([O:8][C:9]1([CH3:30])[CH2:12][N:11]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][C@H:22]([CH2:24][N:25]=[N+]=[N-])[O:21][C:20]3=[O:28])=[CH:15][C:14]=2[F:29])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N#N.N1C=CC=CC=1.[C:39](OC(=O)C)(=[O:41])[CH3:40]>C(OCC)(=O)C.[Pd].CO.C(Cl)(Cl)Cl>[Si:1]([O:8][C:9]1([CH3:30])[CH2:12][N:11]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:23][C@H:22]([CH2:24][NH:25][C:39](=[O:41])[CH3:40])[O:21][C:20]3=[O:28])=[CH:15][C:14]=2[F:29])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 947NitrogenHCID 1049PyridineHCID 7918Acetic AnhydrideHCID 86753891HCID 86753891, compound

Product 1

HCID 70197353HCID 70197353, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolventHCID 21584188Chloroform methanolSolvent

Procedure

A solution of (R)-[[3-[4-[3-[(tert-butyldimethylsilyl)oxy]-3-methyl-1-azetidinyl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]azide (0.750 g, 1.72 mmol) in ethyl acetate (20 mL) was degassed by repeated evacuation and filling with N2. The solution was then treated with 10% palladium/carbon (0.075 g) under a N2 stream. The atmosphere was replaced with H2 (balloon) by repeated evacuation and filling and the reaction mixture stirred at ambient temperature. TLC analysis (5% methanol/chloroform) after 6 h revealed the reduction to be complete. The reaction mixture was filtered through Celite® and the filtrate concentrated under reduced pressure. The residue was dissolved in dry dichloromethane (10 mL), cooled to 0° C. with an ice bath, and treated with pyridine (0.680 g, 0.696 mL, 8.60 mmol) and acetic anhydride (0.263 g, 0.243 mL, 2.58 mmol). The cooling bath was removed and the reaction mixture stirred at ambient temperature under N2. After 3 h the reaction mixture was transferred to a separatory funnel along with dichloromethane (100 mL). The mixture was washed with 10% hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated in vacuo. Radial chromatography over silica gel, eluting with 3% and then 5% methanol/chloroform, afforded, after concentration of appropriate fractions, 0.643 g (83%) of the title compound as a white solid with mp 137°-138° C. and MS(EI) 451 (M+).

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. concentrationthe filtrate concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dry dichloromethane (10 mL)
  4. temperaturecooled to 0° C. with an ice bath
  5. customThe cooling bath was removed
  6. stirringthe reaction mixture stirred at ambient temperature under N2
  7. washThe mixture was washed with 10% hydrochloric acid, saturated aqueous sodium bicarbonate and brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. washRadial chromatography over silica gel, eluting with 3%
  12. custom5% methanol/chloroform, afforded

Sources & evidence

ORD record
ord-9cc4adbaf3134ef2bc111c0b6d097c33
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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