Diisopropylethylamine → 3,3-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine

HRID 1915730Notes

Reaction equation

Cl[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].Cl.[F:12][C:13]1([F:19])[CH2:18][CH2:17][CH2:16][NH:15][CH2:14]1.CCN(C(C)C)C(C)C>CCO>[F:12][C:13]1([F:19])[CH2:18][CH2:17][CH2:16][N:15]([C:2]2[N:6]([CH3:7])[N:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:14]1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of 5-chloro-1-methyl-4-nitro-1H-pyrazole from Example 1 (0.1 g, 4.5 mmol), 3,3-difluoropiperidine hydrochloride (0.14 g, 0.93 mmol) and DIPEA (0.5 mL, 2.8 mmol) in EtOH (3 mL) was heated at 130° C. in a microwave for 1 hr. Additional DIPEA (0.5 mL, 2.8 mmol) and 3,3-difluoropiperidine hydrochloride (0.29 g, 1.8 mmol) were added and the mixture was heated at 130° C. in a microwave for 2 hr. The solvent was removed under reduced pressure and the crude product was purified via silica gel column chromatography (0-60% EtOAc/isohexane) to yield 3,3-difluoro-1-(1-methyl-4-nitro-1H-pyrazol-5-yl)piperidine as a yellow oil (127 mg, 83%). 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 3.80 (s, 3H), 3.41-3.29 (m, 2H), 3.26-3.04 (m, 2H), 2.17-2.03 (m, 2H), 1.97-1.88 (m, 2H).

Workup

temperaturethe mixture was heated at 130° C. in a microwave for 2 hr
customThe solvent was removed under reduced pressure
customthe crude product was purified via silica gel column chromatography (0-60% EtOAc/isohexane)

Sources & evidence

ORD record: ord-f4ded69fb37144e6a825a6f64a6e6fcc
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614206B2

Reaction notes

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