Pyrazole → tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1627572Notes

Reaction equation

HRID 1627572 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.[H-].[Na+].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19](OS(C)(=O)=O)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].N1C=CC=N1>CN(C=O)C.O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([N:4]2[CH:3]=[C:2]([Br:1])[CH:6]=[N:5]2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 163754-BromopyrazoleHCID 24758Sodium hydrideHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 45480278tert-Butyl 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-bromo-pyrazole (10.44 g, 71.03 mmol) in anhydrous DMF (96 mL), cooled to 0° C., was slowly added NaH (60% in mineral oil) (3.13 g, 78.133 mmol). The solution was stirred for 1 hour at 0° C. 4-Methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (19.82 g, 71.03 mmol) was added slowly and the reaction was heated to 100° C. overnight or until consumption of the pyrazole by NMR. The reaction was cooled to room temperature and water added (20 mL) followed by extraction with EtOAc. The combined extracts were washed with saturated aqueous NaCl (4×20 mL), dried with Na2SO4 and concentrated to afford 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as an orange oil. The oil was purified using silica gel chromatography eluting with 10% EtOAc/hexanes to 25% EtOAc/hexanes to provide 4-(4-bromo-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (10.55 g, 45% yield) with a Rf=0.4 (25% EtOAc/hexanes, using iodine as the stain). 1H NMR (CDCl3, 400 MHz) δ 7.46 (s, 1H), 7.43 (s, 1H), 4.23 (m, 3H), 2.88 (m, 2H), 2.10 (m, 2H), 1.88 (m, 2H), 1.47 (s, 9H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionfollowed by extraction with EtOAc
  3. washThe combined extracts were washed with saturated aqueous NaCl (4×20 mL)
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4fbfe1d052dc4dcd97065a2e5dec2d93
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

Loading…