Potassium Carbonate → 6-chloro-5-[4-(oxetan-3-ylmethoxy)phenyl]-1H-indole-3-carbaldehyde

HRID 338439Notes

Reaction equation

HRID 338439 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.[C:19](=O)([O-])[O-:20].[K+].[K+].Br[C:26]1[CH:37]=[CH:36][C:29]([O:30][CH2:31][CH:32]2[CH2:35][O:34][CH2:33]2)=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:19]=[O:20])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:26]1[CH:37]=[CH:36][C:29]([O:30][CH2:31][CH:32]2[CH2:35][O:34][CH2:33]2)=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 601694283-((4-Bromophenoxy)methyl)oxetaneHCID 866987336-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole

Product 1

HCID 866987716-chloro-5-[4-(oxetan-3-ylmethoxy)phenyl]-1H-indole-3-carbaldehydeYield 53.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 217120691,4-dioxane N,N-dimethylformamideSolvent

Procedure

To a sealed tube was added 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole (100 mg, 0.38 mmol) and N,N-dimethylformiminium chloride (97.7 mg, 0.76 mmol) in dioxane/DMF=5/1 (6 mL). The sealed vial was stirred at room temperature for 10 min. to give a white slurry. To the slurry was added 2M potassium carbonate (1.0 mL, 1.9 mmol), 3-[(4-bromophenoxy)methyl]oxetane (92.3 mg, 0.38 mmol) and Pd(dppf)Cl2 (30 mg, 0.05 mmol). The sealed vial was heated to 90° C. for 30 min. TLC (petroleum ether/ethyl acetate=1:1) showed the reaction was complete. The reaction was quenched with water (20 mL), then washed with EtOAc (20 mL×3). The combined organics was dried over sodium sulfate, filtered, concentrated, and purified by combi-flash to give the title compound (70 mg, 53% yield) as a yellow solid. 1H NMR (400 MHz, CD3OD) δ 9.90 (s, 1H), 8.17 (s, 1H), 8.11 (s, 1H), 7.62 (s, 1H), 7.38 (d, 2H) 7.03 (d, 2H), 4.92 (m, 2H), 4.65 (t, 1H), 4.61 (s, 1H), 4.28-4.27 (m, 2H), 3.50 (m, 1H).

Workup

  1. customto give a white slurry
  2. temperatureThe sealed vial was heated to 90° C. for 30 min
  3. customThe reaction was quenched with water (20 mL)
  4. washwashed with EtOAc (20 mL×3)
  5. dry with materialThe combined organics was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by combi-flash

Sources & evidence

ORD record
ord-c1ecc4f36529463e8220e5aae92a42e7
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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