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

HRID 408792Notes

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-b3db0e0751f5460388af25f6350a2059
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759359B2

Reaction notes

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