Sodium hydride → HCID 68538403, compound

HRID 1993660Notes

Reaction equation

HRID 1993660 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[C:23]([CH3:24])=[CH:22][C:21]([N+:25]([O-:27])=[O:26])=[CH:20][N:19]=1>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:18]2[C:23]([CH3:24])=[CH:22][C:21]([N+:25]([O-:27])=[O:26])=[CH:20][N:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 896482-Chloro-3-methyl-5-nitropyridineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 68538403HCID 68538403, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add a suspension of pre-washed NaH (1.27 g, 31.87 mmol, 60% dispersion in mineral oil) in THF (20 mL) to an ice cold solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (6.41 g, 31.87 mmol) in dry THF (80 mL). Allow the mixture to stir for 20 minutes, then add 2-chloro-3-methyl-5-nitro pyridine (5 g, 28.97 mmol) in portions. After addition is completed, remove cooling bath and stir the reaction mixture at 22° C. overnight. Cool the reaction mixture with an ice bath and add a saturated aq. sodium bicarbonate solution (50 mL). Distribute the reaction mixture between ethyl acetate (350 mL) and distilled water (150 mL). Isolate the aqueous phase and extract with ethyl acetate (1×100 mL). Combine organic layers and wash with saturated aq. sodium chloride solution (2×150 mL). Dry the combined organic phases over sodium sulfate and concentrate. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give 4-(3-methyl-5-nitro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (6.5 g, 67% yield). MS(ES): m/z=360.3 [M+Na].

Workup

  1. additionAdd
  2. additionAfter addition
  3. customremove
  4. temperaturecooling bath
  5. stirringstir the reaction mixture at 22° C. overnight
  6. temperatureCool the reaction mixture with an ice bath
  7. additionadd a saturated aq. sodium bicarbonate solution (50 mL)
  8. distillationdistilled water (150 mL)
  9. customIsolate the aqueous phase
  10. extractionextract with ethyl acetate (1×100 mL)
  11. washCombine organic layers and wash with saturated aq. sodium chloride solution (2×150 mL)
  12. dry with materialDry the combined organic phases over sodium sulfate
  13. concentrationconcentrate
  14. washSubject residue to silica gel chromatography eluting with hexanes and ethyl acetate

Sources & evidence

ORD record
ord-9581c7128abf4044b0417ced7a4fecac
Source dataset
uspto-grants-2010_01
Patent number
US07652015B2

Reaction notes

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