Hydrochloric Acid → 6-Chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]-3-methoxyphenyl}-1H-indole-3-carboxylic acid

HRID 338510Notes

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([CH2:25][OH:26])[CH2:24][CH2:23][CH2:22]2)=[C:17]([O:27][CH3:28])[CH:16]=1.Cl>[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:20]=[CH:19][C:18]([C:21]2([CH2:25][OH:26])[CH2:24][CH2:23][CH2:22]2)=[C:17]([O:27][CH3:28])[CH:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The mixture of methyl 6-chloro-5-{4-[1-(hydroxymethyl)cyclobutyl]-3-methoxyphenyl}-1H-indole-3-carboxylate (220 mg, 0.55 mmol) in aqueous sodium hydroxide (10%, 3 mL) and methanol (5 mL) was stirred at 80° C. for 16 hours. The mixture was acidified by concentrated HCl to pH˜4 and extracted with dichloromethane. The organic phases were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to give a residue, which was purified by reverse phase HPLC to give the title compound (25 mg, 12%) as a white solid. MS (AP+) 368.1 (M−H2O+H)+, 408.1 (M+Na)+. 1H NMR (500 MHz, CD3OD) δ 8.03 (s, 1H), 7.98 (s, 1H), 7.57 (s, 1H), 7.08 (d, 1H), 6.98 (d, 2H), 3.86 (s, 2H), 3.80 (s, 3H), 2.36 (m, 4H), 2.11 (m, 1H), 1.86 (m, 1H)

Workup

extractionextracted with dichloromethane
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customto give a residue, which
customwas purified by reverse phase HPLC

Sources & evidence

ORD record: ord-093ef31b7bec46589d01f843ccbab518
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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