Methyl iodide → 2,2,2-trifluoro-N-(6-fluoro-3-methylimidazo[1,2-a]pyridin-2-yl)acetamide

HRID 1473961Notes

Reaction equation

[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]2[C:15]=1I)=[O:4].[Li+].[CH3:20]CC[CH2-].CI>O1CCCC1>[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][N:9]2[C:15]=1[CH3:20])=[O:4]

Participants

Conditions

Temperature: -78 °C

Procedure

2,2,2-trifluoro-N-(6-fluoro-3-iodoimidazo[1,2-a]pyridin-2-yl)acetamide (500 g, 0.00134 mol) was dissolved in tetrahydrofuran (16 mL) and was cooled at −78° C. N-Butyllithium (2 molarin cyclohexane, 1.6 mL) was added and the reaction was warmed to −20 for 15 minutes then chilled to 78° C. Methyl iodide (110 uL, 0.0017 mol) was added and the reaction was allowed to warm to room temperature. The reaction was poured into ice water and extracted with ethyl acetate (3×50 mL). The combined organics were dried (magnesium sulfate) and solvent removed. Residue chromatographed on silica (50% ethyl acetate/hexanes) to give 2,2,2-trifluoro-N-(6-fluoro-3-methylimidazo[1,2-a]pyridin-2-yl)acetamide 5 Rf 0.47, 50% ethyl acetate/hexanes; MS m/z 262 (M+H).

Workup

temperaturethe reaction was warmed to −20 for 15 minutes
temperaturethen chilled to 78° C
temperatureto warm to room temperature
extractionextracted with ethyl acetate (3×50 mL)
dry with materialThe combined organics were dried (magnesium sulfate) and solvent
customremoved
customResidue chromatographed on silica (50% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-ce1d752192d840dbb9b6ab2d9526172b
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018208B2

Reaction notes

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