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

HRID 402891Notes

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-b6854d9fa32a455f97028eb691dae24a
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08742132B2

Reaction notes

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