Acetonitrile → 6-fluoro-5-(2'-hydroxybiphenyl-4-yl)-1H-indole-3-carboxylic acid

HRID 1054845Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])=[CH:15][CH:14]=1.C(#N)C.CC(=CC)C.Cl([O-])=[O:35].[Na+]>O.C(OCC)(=O)C.C(O)(C)(C)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:35])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A round bottomed flask was charged with 6-fluoro-5-(2′-hydroxybiphenyl-4-yl)-1H-indole-3-carbaldehyde (20 mg, 0.60 mmol), acetonitrile, (1.0 mL), t-butanol (1.0 mL) and cooled to 0° C. 2-methyl-2-butene (0.49 mL, 4.6 mmol) was then added. In a separate flask, sodium chlorite (102 mg, 1.20 mmol) and NaH2PO4 (170 mg, 1.23 mmol) were dissolved in water (1 mL) then added to the reaction. The reaction was sealed and reacted at room temperature for 15 h. Ethyl acetate and water were added and the layers were separated. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Reverse phase HPLC was then used to provide the title compound (8.4 mg, 40%). MS (ES−) 346.1 (M−H)−. Retention time: 1.86 min Waters Xbridge dC18 5 um 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

additionthen added to the reaction
customThe reaction was sealed
customreacted at room temperature for 15 h
customthe layers were separated
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b114122de4d949ef97073800c9e6cb98
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394285B2

Reaction notes

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