Cesium carbonate → Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1844185Notes

Reaction equation

Cl[CH2:2][C:3]1[C:8]([F:9])=[CH:7][N:6]=[CH:5][C:4]=1[F:10].C(=O)([O-])[O-].[Cs+].[Cs+].[OH:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1>CN(C=O)C.O>[F:10][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([F:9])[C:3]=1[CH2:2][O:17][C:18]1[C:19]2[N:20]([C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:25]([CH3:27])[N:26]=2)[CH:21]=[CH:22][CH:23]=1

Participants

Conditions

Temperature: 60 °C

Procedure

At RT, 1.86 g of 4-(chloromethyl)-3,5-difluoropyridine (Example 115A, 9.1 mmol, 2.0 equivalent) and 4.44 g of caesium carbonate (13.6 mmol, 3 equivalent) were added to 1.0 g of ethyl 8-hydroxy-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 3A, 4.54 mmol, 1.0 equivalent) in 100 ml of DMF, and the mixture was stirred at 60° C. for 1 h. The mixture was then diluted with 500 ml of water and extracted twice with in each case 300 ml of ethyl acetate. The combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated using a rotary evaporator. The residue obtained was purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1). This gave 900 mg (54% of theory) and 200 mg (13% of theory; purity about 85%) of the title compound.

Workup

extractionextracted twice with in each case 300 ml of ethyl acetate
washThe combined organic phases were washed with 400 ml of saturated aqueous sodium chloride solution
dry with materialdried over sodium sulphate
concentrationconcentrated
customa rotary evaporator
customThe residue obtained
customwas purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 7:1 to 1:1)

Sources & evidence

ORD record: ord-01ae87594b5c40dcb2b0eac28b45d450
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946215B2

Reaction notes

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