Potassium Carbonate → 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]-N-methylacetamide

HRID 1054764

Reaction equation

HRID 1054764 reaction equation
CO[C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:22])=[C:11](B3OCC(C)(C)CO3)[CH:12]=2)[NH:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].Br[C:30]1[CH:41]=[CH:40][C:33]([O:34][CH2:35][C:36]([NH:38][CH3:39])=[O:37])=[CH:32][CH:31]=1>>[Cl:22][C:10]1[CH:9]=[C:8]2[C:13]([C:5]([CH:3]=[O:4])=[CH:6][NH:7]2)=[CH:12][C:11]=1[C:30]1[CH:41]=[CH:40][C:33]([O:34][CH2:35][C:36]([NH:38][CH3:39])=[O:37])=[CH:32][CH:31]=1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 75350232-(4-bromophenoxy)-N-methylacetamideHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate

Product 1

HCID 866987562-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]-N-methylacetamideYield 72.9%

Conditions

Temperature
90 °C

Procedure

To the slurry of methyl-6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (240 mg, 1.0 mmol) was added 2 M potassium carbonate (2.5 mL, 5.0 mmol), 2-(4-bromophenoxy)-N-methylacetamide (240 mg, 1.00 mmol) and PddppfCl2 (50 mg, 0.061 mmol). The sealed vial was heated to 90° C. for 30 min. The reaction was cooled to room temperature and quenched with water (20 mL), and then washed three times with ethyl acetate (20 mL). The combined organics were dried and concentrated to give the title compound (250 mg, 55% yield) as a yellow solid that was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 9.94 (s, 1H), 8.37 (d, 1H), 8.02 (s, 1H), 7.68 (s, 1H), 7.38 (d, 2H), 7.05 (d, 2H), 4.52 (s, 2H), 2.68 (d, 3H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with water (20 mL)
  3. washwashed three times with ethyl acetate (20 mL)
  4. customThe combined organics were dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-afc1d5eae2534beeb0de762c66178d6b
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Linked notes

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