Sodium Hydroxide → 6-chloro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid

HRID 338384Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[OH:27])=[CH:17][CH:16]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[OH:27])=[CH:19][CH:20]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A round bottomed flask was charged with methyl 6-chloro-5-(2′-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylate (80 mg, 0.21 mmol), methanol (1.8 mL), and sodium hydroxide solution (1.0M, 0.60 mL, 0.60 mmol) then heated to 70° C. with stirring for 15 h. The reaction was then cooled to room temperature and quenched with 1.0M Hydrochloric acid and diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate (x3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase HPLC was then used to provide the title compound (13 mg, 16% yield). MS (ES−) 362.0 (M−H)−. Retention time: 1.93 min Waters Xbridge dC18 5 μm 4.6×50 mm, 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. (0.03% NH4OH). Flow: 2.0 mL/min.

Workup

temperatureThe reaction was then cooled to room temperature
customquenched with 1.0M Hydrochloric acid
additiondiluted with ethyl acetate
customThe layers were separated
extractionthe aqueous extracted with ethyl acetate (x3)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5445b42d5a224a1a80a6cb60f9646b04
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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