Ethyl 2-(6-cyanoimidazo[1,2-a]pyridin-3-yl)acetate → Ethyl 2-(6-formylimidazo[1,2-a]pyridin-3-yl)acetate

HRID 216672Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([C:15]#N)[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2].O.[PH2]([O-])=[O:20].[Na+]>O.N1C=CC=CC=1.C(O)(=O)C.[Ni]>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[N:10]2[CH:11]=[C:12]([CH:15]=[O:20])[CH:13]=[CH:14][C:9]2=[N:8][CH:7]=1)[CH3:2]

Participants

Conditions

Temperature: 75 °C

Procedure

(6-Cyano-imidazo[1,2-a]pyridin-3-yl)-acetic acid ethyl ester (1.80 g, 7.46 mmol) is dissolved in a mixture of water (5.0 ml), pyridine (10 ml) and glacial acetic acid (5.0 ml). Sodium hypophosphite monohydrate (6.03 g, 56.4 mmol, 8 equiv) and Raney nickel (approx. 1.2 g) are added at room temperature. The reaction mixture is heated to 75° C. for 1 h, cooled to room temperature and filtered through Celite. The filtrate is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via flash chromatography (cylcohexane/EtOAc 1:1, +0.1% NEt3) affords the title compound (770 mg, 42%). 1H NMR (400 MHz, CDCl3): δ=10.01 (s, 1H), 8.69 (s, 1H), 7.73 (s, 1H), 7.72 (s, 1H), 7.69 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 4.04 (s, 2H), 1.30 (t, J=7.4 Hz, 3H). MS (ES+): 233 (M+H)+.

Workup

temperaturecooled to room temperature
filtrationfiltered through Celite
extractionThe filtrate is extracted three times with EtOAc
washThe combined organic layers are washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the residue via flash chromatography (cylcohexane/EtOAc 1:1, +0.1% NEt3)

Sources & evidence

ORD record: ord-70978bf13723437f8219e96ea6cfa4e3
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193236B2

Reaction notes

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