Potassium Carbonate → (S)-6-(2-methylpyrrolidin-1-yl)-3-nitro-2-(trifluoromethyl)pyridine

HRID 1915503Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH3:26][C@H:27]1[CH2:31][CH2:30][CH2:29][NH:28]1.C([O-])([O-])=O.[K+].[K+]>O>[CH3:26][C@H:27]1[CH2:31][CH2:30][CH2:29][N:28]1[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A suspension of 6-bromo-3-nitro-2-(trifluoromethyl)pyridine (400 mg, 1.5 mmoL), (S)-2-methylpyrrolidine tosylate salt (381 mg, 1.5 mmoL) and K2CO3 (620 mg, 4.5 mmoL) in H2O (4 mL) was heated at 140° C. under microwave irradiation for 30 minutes. The solution was extracted with EtOAc (50 mL×3) and the combined organic layer was washed with brine, dried over anhydrous Na2SO4 and purified by silica gel column chromatography to afford (S)-6-(2-methylpyrrolidin-1-yl)-3-nitro-2-(trifluoromethyl)pyridine (350 mg, 88% yield). 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=9.2 Hz, 1H), 6.44 (d, J=8.4 Hz, 1H), 4.55-4.42 (m, 1H), 4.02-3.30 (m, 2H), 2.30-2.00 (m, 3H), 1.81 (brs, 1H), 1.27 (d, J=6.4 Hz, 3H).

Workup

extractionThe solution was extracted with EtOAc (50 mL×3)
washthe combined organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
custompurified by silica gel column chromatography

Sources & evidence

ORD record: ord-9367d5f94bd14d3fafa65fb6a2021533
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614327B2

Reaction notes

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