Hydrochloric Acid → 1-[3-(3,5-Difluorophenyl)-5-methylimidazo[1,2-a]pyridin-2-yl]ethanone

HRID 1478682Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[C:14]([CH3:18])=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:19](N(OC)C)=[O:20])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:25][Mg]Cl.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[C:14]([CH3:18])=[CH:15][CH:16]=[CH:17][C:12]3=[N:11][C:10]=2[C:19](=[O:20])[CH3:25])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3-(3,5-difluorophenyl)-N-methoxy-N,5-dimethylimidazo[1,2-a]pyridine-2-carboxamide (0.43 g, 1.3 mmol) in tetrahydrofuran (5.2 mL) at 0° C. was treated with 3 M methylmagnesium chloride in tetrahydrofuran (1.3 mL, 3.9 mmol) dropwise and stirred at 0° C. for 30 min. The reaction mixture was treated with additional 3 M methylmagnesium chloride in tetrahydrofuran (1.3 mL, 3.9 mmol) dropwise and stirred at 0° C. for another 30 min. The reaction mixture was quenched with 1 M hydrogen chloride (5.2 mL, 5.2 mmol), poured into saturated sodium bicarbonate (25 mL), and extracted with ethyl acetate (75 mL). The organic layer was separated, washed with brine and water, and dried with sodium sulfate, filtered, and concentrated to a crude solid. Purification by flash column chromatography gave the desired product (0.29 g, 78%). LCMS for C16H13F2N2O (M+H)+: m/z=287.1.

Workup

stirringstirred at 0° C. for another 30 min
extractionextracted with ethyl acetate (75 mL)
customThe organic layer was separated
washwashed with brine and water
dry with materialdried with sodium sulfate
filtrationfiltered
concentrationconcentrated to a crude solid
customPurification by flash column chromatography

Sources & evidence

ORD record: ord-1461654f78fa4199973123ac8b2e342a
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403847B2

Reaction notes

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