Sodium hydride → tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate

HRID 2090295Notes

Reaction equation

HRID 2090295 reaction equation
[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[H-].[Na+].[N:17]1([C:23]([O-:25])=[O:24])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>CN(C)C=O>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH:20]3[CH2:21][CH2:22][N:17]([C:23]([O:25][C:2]([CH3:14])([CH3:6])[CH3:1])=[O:24])[CH2:18][CH2:19]3)[CH:10]=2)[O:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 21874245Piperidine carboxylate

Product 1

HCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateYield 57.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4.12 g, 21.2 mmol, Aldrich, Cat. 525057) in N,N-dimethylformamide (20 mL) was added sodium hydride (1.78 g, 44.5 mmol) at 0° C. The resulting solution was stirred at r.t. for one hour, and then tert-butyl 4-[methylsulfonyl)oxy]piperidine-1-carboxylate (6.3 g, 22 mmol) in DMF (2 mL) was added. The reaction mixture was heated at 90° C. overnight. Then the reaction mixture was cooled to r.t., quenched with water, and extracted with AcOEt. The organic layer was washed with NaHCO3 aqueous solution and brine successively, dried with MgSO4, and concentrated. The residue was purified by flash column chromatography on a silica gel column using 30% ethyl acetate in hexane as eluent to afford the desired compound (2.30 g, 28.74%). LCMS (M+H)+: m/z=378.4.

Workup

  1. temperatureThe reaction mixture was heated at 90° C. overnight
  2. temperatureThen the reaction mixture was cooled to r.t.
  3. customquenched with water
  4. extractionextracted with AcOEt
  5. washThe organic layer was washed with NaHCO3 aqueous solution and brine successively
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on a silica gel column

Sources & evidence

ORD record
ord-2c01986f20554ce59a259f424cc8a037
Source dataset
uspto-grants-2013_05
Patent number
US08436008B2

Reaction notes

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