Ethyl (chloroformyl)acetate → Ethyl 7-iodo-6-methylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1748199Notes

Reaction equation

[I:1][C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([NH2:9])[CH:3]=1.C(=O)(O)[O-].[Na+].Cl[CH:16]([CH:22]=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18]>C(COC)OC.ClCCl>[I:1][C:2]1[C:7]([CH3:8])=[CH:6][N:5]2[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:22][N:9]=[C:4]2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 4-iodo-5-methylpyridin-2-amine (I-28A) (1.55 g. 6.6 mmol), sodium bicarbonate (0.67 g, 7.9 mmol) in dry dimethoxyethane (10 mL) at room temperature, ethyl 2-chloro-3-oxopropanoate (1 g, 6.41 mmol) in dimethoxyethane (1 mL) was added dropwise. The reaction mixture was heated to 100° C. for 1 h and then cooled to room temperature and diluted with dichloromethane (50 mL). The organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo. The brown crude oil was purified by silica gel chromatography with a gradient of 0-15% ethyl acetate/hexanes to yield ethyl 7-iodo-6-methylimidazo[1,2-a]pyridine-3-carboxylate (I-28B) as light tan solid. 1H-NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 8.41 (s, 1H), 8.22 (s, 1H), 4.36 (q, J=7.2 Hz, 2H), 2.42 (s, 3H), 1.37 (t, J=7.2 Hz, 3H). MS m/z 331.0 (M+1).

Workup

temperaturecooled to room temperature
washThe organic layer was washed with water, brine
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe brown crude oil was purified by silica gel chromatography with a gradient of 0-15% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-5549f69cc4a043b0b40e6aa6599c2f50
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09150568B2

Reaction notes

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