Nitrogen → (S)-N-[[3-[3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1418658Notes

Reaction equation

HRID 1418658 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:15]([O-])=O)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:11][C:10]([O:13][CH3:14])([CH3:12])[CH2:9]1.[N:18]#N.[CH:20]([O-:22])=[O:21].[NH4+].C(=O)(O)[O-].[Na+].ClC(OC[C:34]1[CH:39]=[CH:38]C=CC=1)=O.[O:40]1CC[CH2:42][CH2:41]1.CO>CC(C)=O.O.[Pd].ClCCl>[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:34][C@H:39]([CH2:38][NH:18][C:41](=[O:40])[CH3:42])[O:21][C:20]2=[O:22])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:11][C:10]([O:13][CH3:14])([CH3:12])[CH2:9]1

Participants

10

Reactant 6

HCID 947NitrogenHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 2723923Ammonium formateHCID 21899815MeOH tetrahydrofuranHCID 544553723-Fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzene

Product 1

HCID 53853142(S)-N-[[3-[3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideYield 89%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A solution of 3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzene (1.60 g, 6.7 mmol) in 25% tetrahydrofuran/methanol (35 mL) was degassed by repeated evacuation and filling with N2 and then treated with 10% palladium/carbon (0.160 g). Ammonium formate (2.10 g, 33.3 mmol) was then added and the mixture degassed a final time. The reaction mixture was stirred at ambient temperature for 20 minutes, during which time the yellow reaction mixture became colorless. TLC analysis (2:1 hexane/ethyl acetate) revealed the reduction to be complete. The reaction mixture was filtered through Celite® (dichloromethane and methanol wash) and the filtrate concentrated in vacuo to give a purple gum that was immediately dissolved in 1:1 acetone/water (30 mL) under N2. The mixture was cooled with an ice bath to 0° C. and treated with sodium bicarbonate (1.10 g, 13.4 mmol) and benzyl chloroformate (1.20 g, 1.00 mL, 7.37 mmol). The cooling bath was allowed to dissipate over a 3 h period. After stirring a further 2 h at ambient temperature, the reaction mixture was transferred to a separatory funnel with dichloromethane (50 mL). The organic phase was separated, washed with water, dried over sodium sulfate, filtered and concentrated in vacuo to give a purple oil. Chromatography over silica gel, eluting with 6:1 hexane/ethyl acetate, afforded, after concentration of appropriate fractions, 2.04 g (89%) of the title compound as a viscous oil which solidified on standing to a waxy solid with mp 73°-75° C. and MS(EI) 344 (M+). Step 4: (R)-[3-[3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol

Workup

  1. customthe mixture degassed a final time
  2. filtrationThe reaction mixture was filtered through Celite® (dichloromethane and methanol wash)
  3. concentrationthe filtrate concentrated in vacuo
  4. customto give a purple gum that
  5. temperatureThe mixture was cooled with an ice bath to 0° C.
  6. waitto dissipate over a 3 h period
  7. stirringAfter stirring a further 2 h at ambient temperature
  8. customThe organic phase was separated
  9. washwashed with water
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a purple oil
  14. washChromatography over silica gel, eluting with 6:1 hexane/ethyl acetate
  15. customafforded

Sources & evidence

ORD record
ord-6d782ad86fd44afb848be30216fcb52f
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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