Lithium Hydroxide → cis(+/-)-2-(Acetylamino)-5-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)benzoic acid

HRID 1425273Notes

Reaction equation

[C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][C@H:18]([NH:21][C:22]([C:24]3[NH:25][C:26]([CH2:30][CH3:31])=[C:27]([Cl:29])[N:28]=3)=[O:23])[C@H:17]([O:32][CH3:33])[CH2:16]2)=[CH:11][C:6]=1[C:7]([O:9]C)=[O:8])(=[O:3])[CH3:2].[OH-].[Li+]>CO.C1COCC1>[C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][C@H:18]([NH:21][C:22]([C:24]3[NH:25][C:26]([CH2:30][CH3:31])=[C:27]([Cl:29])[N:28]=3)=[O:23])[C@H:17]([O:32][CH3:33])[CH2:16]2)=[CH:11][C:6]=1[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

Methyl cis(±)-2-(acetylamino)-5-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)benzoate obtained in Example (185e) (120 mg) was dissolved in methanol (4 ml) and THF (4 ml). A 2 N aqueous lithium hydroxide solution (2 ml) was added, and the mixture was stirred at 70° C. for one hour. The organic solvent was evaporated under reduced pressure, followed by neutralization with 1 N hydrochloric acid and extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was recrystallized from an ethyl acetate/methanol/hexane solvent to obtain 90 mg of the title compound as crystals.

Workup

customThe organic solvent was evaporated under reduced pressure
extractionfollowed by neutralization with 1 N hydrochloric acid and extraction with ethyl acetate
dry with materialThe organic layer was dried over anhydrous sodium sulfate
concentrationconcentration under reduced pressure
customthe residue was recrystallized from an ethyl acetate/methanol/hexane solvent

Sources & evidence

ORD record: ord-234000931ace46a1a9586cf61069fa24
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927588B2

Reaction notes

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