Sodium hydride → tert-Butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 590619Notes

Reaction equation

HRID 590619 reaction equation
[H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.S([CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)(C)(=O)=O>CN(C=O)C>[I:3][C:4]1[CH:5]=[N:6][N:7]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 770224-IodopyrazoleHCID 22504298Tert-butyl 4-(methylsulfonyl)piperidine-1-carboxylate

Product 1

HCID 45480389tert-Butyl 4-(4-iodo-1H-pyrazol-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (60% suspension, 1.13 g, 28.4 mmol) was added portion wise to a solution of 4-iodopyrazole (5 g, 25.7 mmol) in anhydrous DMF (30 mL) at 0° C.; and it was stirred for 1 h. Finally, tert-butyl 4-mesylpiperidine-1-carboxylate (CAS: 141699-59-4) (6.5 g, 32.7 mmol) was added to the reaction mixture and it was stirred at 100° C. for 16 h. It was, then, cooled and quenched with saturated solution of NH4Cl (100 mL). Extraction was carried out using EtOAc (50 mL×2); the combined organic layers were washed with water (100 mL); brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide crude product, which was further purified by silica gel column chromatography (20% EtOAc in hexanes) to give title compound Va-1-I (4 g, 41%). LCMS: m/z 378.1 (M+1)+.

Workup

  1. stirringwas stirred at 100° C. for 16 h
  2. temperaturecooled
  3. customquenched with saturated solution of NH4Cl (100 mL)
  4. extractionExtraction
  5. washthe combined organic layers were washed with water (100 mL)
  6. dry with materialbrine (100 mL), dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide crude product, which
  10. customwas further purified by silica gel column chromatography (20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d08cedf8e3774f68b0ba93e501c60ab2
Source dataset
uspto-grants-2016_01
Patent number
US09233983B2

Reaction notes

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