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

HRID 1512083Notes

Reaction equation

[H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.[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]>CN(C=O)C>[I:3][C:4]1[CH:5]=[N:6][N:7]([CH:19]2[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:17][CH2:18]2)[CH:8]=1

Participants

Conditions

Temperature: 4 °C

Procedure

NaH (1.2 eq., 0.68 mmol) was added portionwise to a stirred solution of 4-iodopyrazole (0.57 mmol) in DMF (2 L) at 4° C. The resulting mixture was stirred for 1 hour at 4° C. and 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester, compound 2 (1.1 eq., 0.63 mmol) was then added. The resulting mixture was heated to 100° C. for 12 h. The reaction was quenched with H2O and extracted with EtOAc several times. The combined organic layers were dried, filtered, and concentrated to afford an orange oil. The residue was purified by silica gel chromatography (eluting with 5% EtOAc in pentane) to give compound 3 as a white solid (140 g, 66%).

Workup

temperatureThe resulting mixture was heated to 100° C. for 12 h
customThe reaction was quenched with H2O
extractionextracted with EtOAc several times
customThe combined organic layers were dried
filtrationfiltered
concentrationconcentrated
customto afford an orange oil
customThe residue was purified by silica gel chromatography (eluting with 5% EtOAc in pentane)

Sources & evidence

ORD record: ord-930b525e8d9641419af0285ef9677ece
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217057B2

Reaction notes

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