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

HRID 2241389Notes

Reaction equation

HRID 2241389 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.CN(C=O)C.[H-].[Na+].CS(O[CH:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)(=O)=O>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:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)[CH:10]=2)[O:3]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateYield 29.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 1 L, 1-neck flask was charged with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (20.0 g, 103 mmol), and DMF (250 mL). The reaction mixture was cooled to 0° C. and NaH (2.73 g, 108 mmol) (95%) was added. The reaction mixture was stirred at 0° C. for 1 hour. tert-Butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (30.2 g, 108 mmol; prepared as in WO 06/021881) was added and the reaction mixture was heated at 100° C. overnight. The reaction mixture was cooled to ambient temperature and diluted with water. The reaction mixture was extracted with EtOAc, and the organic layer washed with brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified on a Biotage 40S column eluting with EtOAc/Hexane 10% to 25% EtOAc. The product was isolated as a white solid (11.3 g, 29%).

Workup

  1. temperaturethe reaction mixture was heated at 100° C. overnight
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. extractionThe reaction mixture was extracted with EtOAc
  4. washthe organic layer washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified on a Biotage 40S column
  9. washeluting with EtOAc/Hexane 10% to 25% EtOAc

Sources & evidence

ORD record
ord-8ba17e2f8e8f4c0cac94491ae958d83c
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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