N-Fluorobenzenesulfonimide → 1-benzyl-4-(4-bromo-5-fluoro-1H-pyrazol-1-yl)piperidine

HRID 1051741Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]([N:22]2[CH:26]=[C:25]([Br:27])[CH:24]=[N:23]2)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[F:28]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O>C1COCC1>[CH2:9]([N:16]1[CH2:21][CH2:20][CH:19]([N:22]2[C:26]([F:28])=[C:25]([Br:27])[CH:24]=[N:23]2)[CH2:18][CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of lithium diisopropylamide (1.0 M in THF/hexanes) (1.25 mL, 1.25 mmol) was slowly added to a −78° C. solution of 1-benzyl-4-(4-bromo-1H-pyrazol-1-yl)piperidine (200 mg, 0.625 mmol) in THF (2.0 mL), and the reaction was allowed to stir at −78° C. for 1 hour. N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (295 mg, 0.937 mmol) was added, and the reaction stirred for an additional 1 hour at −78° C. The reaction was quenched via the addition of saturated aqueous ammonium chloride (5 mL). The reaction was warmed to room temperature and concentrated in vacuo. Ethyl acetate (25 mL) was added, and the organic solution was washed with water (2×10 mL) and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified directly via column chromatography on silica gel (Biotage 25 g column, gradient elution with 20-30% ethyl acetate in hexanes) to afford 1-benzyl-4-(4-bromo-5-fluoro-1H-pyrazol-1-yl)piperidine (53 mg, 25%) as a light yellow oil. MS (ESI, pos. ion) m/z 339 [M+H]+.

Workup

stirringthe reaction stirred for an additional 1 hour at −78° C
customThe reaction was quenched via the addition of saturated aqueous ammonium chloride (5 mL)
temperatureThe reaction was warmed to room temperature
concentrationconcentrated in vacuo
additionEthyl acetate (25 mL) was added
washthe organic solution was washed with water (2×10 mL) and brine (10 mL)
dry with materialThe organic layer was dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified directly via column chromatography on silica gel (Biotage 25 g column, gradient elution with 20-30% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-cb5e60107ccf463c8f418edff5b78bdf
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388161B2

Reaction notes

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