Potassium Carbonate → Methyl 6-chloro-5-(4-(1-(hydroxymethyl)cyclobutyl)-3-methoxyphenyl)-1h-indole-3-carboxylate

HRID 338509Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:12][OH:13])[CH2:11][CH2:10][CH2:9]2)=[C:4]([O:14][CH3:15])[CH:3]=1.[Cl:16][C:17]1[CH:25]=[C:24]2[C:20]([C:21]([C:26]([O:28][CH3:29])=[O:27])=[CH:22][NH:23]2)=[CH:19][C:18]=1B1OCC(C)(C)CO1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[Cl:16][C:17]1[CH:25]=[C:24]2[C:20]([C:21]([C:26]([O:28][CH3:29])=[O:27])=[CH:22][NH:23]2)=[CH:19][C:18]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:12][OH:13])[CH2:11][CH2:10][CH2:9]2)=[C:4]([O:14][CH3:15])[CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of [1-(4-bromo-2-methoxyphenyl)cyclobutyl]methanol (180 mg, 0.660 mmol) in dioxane (10 mL) and water (4 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (213 mg, 0.660 mmol), Pd (dppf)Cl2 (48 mg, 0.070 mmol) and potassium carbonate (273 mg, 2.00 mmol). The reaction mixture was purged with nitrogen for 3 minutes and stirred at 80° C. for 2 hours. The mixture was extracted with dichloromethane. The organic phases were combined, dried over sodium sulfate, filtered, and concentrated in vacuo to give the title compound (220 mg, 83%) as a brown solid. It was used for next step without further purification.

Workup

customThe reaction mixture was purged with nitrogen for 3 minutes
extractionThe mixture was extracted with dichloromethane
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-bd70a4a666a64d8d8b3b754a95778537
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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