Water → 3-Fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzoic acid

HRID 909504Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[C:17]([C:19]2[NH:20][C:21]([C:24]3[S:25][CH:26]=[CH:27][N:28]=3)=[CH:22][CH:23]=2)[CH:16]=[C:15]([O:29][C@@H:30]([CH3:34])[CH2:31][O:32][CH3:33])[CH:14]=1)[C:5]([O:7]C)=[O:6].O.O.[OH-].[Li+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[C:17]([C:19]2[NH:20][C:21]([C:24]3[S:25][CH:26]=[CH:27][N:28]=3)=[CH:22][CH:23]=2)[CH:16]=[C:15]([O:29][C@@H:30]([CH3:34])[CH2:31][O:32][CH3:33])[CH:14]=1)[C:5]([OH:7])=[O:6]

Participants

Conditions

Temperature: 60 °C

Procedure

Methyl 3-fluoro-4-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}benzoate (611 mg, 1.42 mmol) synthesized in Example 43 was dissolved in methanol (18 mL), and water (3 mL) and lithium hydroxide monohydrate (298 mg, 7.10 mmol) were added, followed by stirring at 60° C. for 4 hours under nitrogen atmosphere. To the reaction solution, water (50 mL) was added, and extraction was carried out twice with ethyl acetate (40 mL), followed by drying over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-75%) to afford the desired compound (519 mg, yield 88%) as a white solid.

Workup

extractionextraction
dry with materialby drying over sodium sulfate
distillationThe solvent was distilled off under reduced pressure
customthe resulting residue was purified
washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=30%-75%)

Sources & evidence

ORD record: ord-8450bbe1b4c94debba379cc8553b0c1f
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08017610B2

Reaction notes

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