Hydrochloric Acid → 6-Cyclopropyl-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

HRID 1844152Notes

Reaction equation

[CH:1]1([C:4]2[CH:5]=[C:6]([O:19][CH2:20][C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])[C:7]3[N:8]([C:10]([C:14]([O:16]CC)=[O:15])=[C:11]([CH3:13])[N:12]=3)[CH:9]=2)[CH2:3][CH2:2]1.[OH-].[Li+].Cl>O1CCCC1.CO>[CH:1]1([C:4]2[CH:5]=[C:6]([O:19][CH2:20][C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])[C:7]3[N:8]([C:10]([C:14]([OH:16])=[O:15])=[C:11]([CH3:13])[N:12]=3)[CH:9]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 40 °C

Procedure

470 mg of ethyl 6-cyclopropyl-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 41A) were initially charged in 36 ml of tetrahydrofuran/methanol 5:1, and 6.1 ml of 1N aqueous lithium hydroxide solution were added. The mixture was stirred at 40° C. for 4 h and then acidified with 6 N hydrochloric acid and concentrated. The residue was taken up in water and repeatedly extracted with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried with magnesium sulphate and filtered, and the filtrate was concentrated. This gave 470 mg of the desired product (90% pure; 97% of theory) which was reacted without further purification.

Workup

additionwere added
concentrationconcentrated
extractionrepeatedly extracted with dichloromethane
washThe combined organic phases were washed with saturated aqueous sodium chloride solution
dry with materialdried with magnesium sulphate
filtrationfiltered
concentrationthe filtrate was concentrated
customThis gave 470 mg of the desired product (90% pure; 97% of theory) which was reacted without further purification

Sources & evidence

ORD record: ord-51125c6f1e7a45ecb3054827232c4256
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946215B2

Reaction notes

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