Sodium hydride → HCID 45786893, compound

HRID 1993658Notes

Reaction equation

HRID 1993658 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1.C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 783082-Chloro-5-nitropyridineHCID 516892Sodium BicarbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 45786893HCID 45786893, compoundYield 75.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Add a suspension of pre-washed NaH (0.1 g, 2.48 mmol, 60% dispersion in mineral oil) in THF (2 mL) to an ice cold solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 2.48 mmol) in dry THF (3 mL). Allow mixture to stir for 20 minutes, then add 2-chloro-5-nitro-pyridine (0.36 g, 2.26 mmol) in portions. After addition is completed, remove cooling bath and stir the reaction mixture at 22° C. overnight. Cool reaction mixture with ice bath and add a saturated aq. sodium bicarbonate solution (5 mL). Distribute the reaction mixture between ethyl acetate (25 mL) and distilled water (25 mL). Isolate the aqueous phase and extract with ethyl acetate (3×35 mL). Dry the combined organic phases over sodium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give 4-(5-Nitro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (0.55 g, 75% yield). MS(ES): m/z=324.2 [M+H].

Workup

  1. additionAdd
  2. additionAfter addition
  3. customremove
  4. temperaturecooling bath
  5. stirringstir the reaction mixture at 22° C. overnight
  6. temperatureCool
  7. customreaction mixture with ice bath
  8. distillationdistilled water (25 mL)
  9. customIsolate the aqueous phase
  10. extractionextract with ethyl acetate (3×35 mL)
  11. dry with materialDry the combined organic phases over sodium sulfate
  12. concentrationconcentrate under reduced pressure
  13. washSubject residue to silica gel chromatography eluting with hexanes and ethyl acetate

Sources & evidence

ORD record
ord-492eacfe419f4c97b3a883237b3d53cd
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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