Sodium hydride → HCID 58732860, compound

HRID 1726366Notes

Reaction equation

HRID 1726366 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:15]2[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[C:17]([F:24])[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].FC1C=C([N+]([O-])=O)C=C(F)C=1>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@H:10]([O:14][C:15]2[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[C:17]([F:24])[CH:16]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 752721,3-Difluoro-5-nitrobenzeneHCID 57433447HCID 57433447, compound

Product 1

HCID 58732860HCID 58732860, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3-(3-Fluoro-5-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. A 3 L 3-neck round bottom flask was charged with sodium hydride (60% in oil, 54.24 g, 1.356 mol) and DMF (1 L). The flask was cooled in an ice bath, a solution of (S)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester alcohol (210 g, 1.043 mol) in DMF (500 mL) was added dropwise over 30 minutes to the flask, maintaining an internal temperature below 5° C. The solution was stirred for 1 hour, then was added via a canula into a 5 L 3-neck round bottom flask charged with a solution of 3,5-difluoronitrobenzene (169.25 g, 1.064 mol) that was cooled in an ice bath. The addition lasted for 1 hour, maintaining an internal temperature below 5° C. The reaction mixture was warmed to room temperature and stirred for 4 hours and diluted with 6 L ethyl acetate. The organic layer was washed with saturated ammonium chloride (4 L), sodium bicarbonate (2 L) and brine (2 L), dried (Na2SO4) and concentrated to afford the desired product (S)-3-(3-fluoro-5-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester as an syrup (360 g, purity ˜95%).

Workup

  1. temperatureThe flask was cooled in an ice bath
  2. temperaturemaintaining an internal temperature below 5° C
  3. additionwas added via a canula into a 5 L 3-neck round bottom flask
  4. temperaturewas cooled in an ice bath
  5. additionThe addition
  6. waitlasted for 1 hour
  7. temperaturemaintaining an internal temperature below 5° C
  8. stirringstirred for 4 hours
  9. washThe organic layer was washed with saturated ammonium chloride (4 L), sodium bicarbonate (2 L) and brine (2 L)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-4660f711f7c3474d91f15979d5a28091
Source dataset
uspto-grants-2009_02
Patent number
US07491826B2

Reaction notes

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