Potassium Carbonate → methyl 5-[4-(1-acetylpiperidin-4-yl)phenyl]-6-chloro-1H-indole-3-carboxylate

HRID 1054719Notes

Reaction equation

HRID 1054719 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:17][O:18][C:19]([C:21]1[C:29]2[C:24](=[CH:25][C:26]([Cl:38])=[C:27](B3OCC(C)(C)CO3)[CH:28]=2)[NH:23][CH:22]=1)=[O:20].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[C:14]([N:11]1[CH2:12][CH2:13][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:27]3[CH:28]=[C:29]4[C:24](=[CH:25][C:26]=3[Cl:38])[NH:23][CH:22]=[C:21]4[C:19]([O:18][CH3:17])=[O:20])=[CH:3][CH:4]=2)[CH2:9][CH2:10]1)(=[O:16])[CH3:15]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 842096201-(4-(4-Bromophenyl)piperidin-1-yl)ethanoneHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate

Product 1

HCID 86698718methyl 5-[4-(1-acetylpiperidin-4-yl)phenyl]-6-chloro-1H-indole-3-carboxylateYield 83.4%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-[4-(4-bromophenyl)piperidin-1-yl]ethanone (200 mg, 0.70 mmol) in 1,4-dioxane/H2O (5 mL/1 mL) was added methyl-6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (183 mg, 1.20 mmol), potassium carbonate (270 mg, 2.10 mmol) and PddppfCl2 (50 mg, 0.070 mmol). The reaction mixture was degassed with nitrogen and the mixture was heated to 90° C. for 30 minutes. The reaction was concentrated under reduced pressure to give a crude product. The material was partitioned between water (20 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous layer was washed two additional times with ethyl acetate (30 mL). The combined organics layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to to give the title compound (240 mg, 83% yield) which was used in the next step without further purification.

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. concentrationThe reaction was concentrated under reduced pressure
  3. customto give a crude product
  4. customThe material was partitioned between water (20 mL) and ethyl acetate (20 mL)
  5. customThe layers were separated
  6. washthe aqueous layer was washed two additional times with ethyl acetate (30 mL)
  7. dry with materialThe combined organics layers were dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e6f6a96c841a405c80f17b1911396c95
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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