Methanol → HCID 23159943, compound

HRID 2110849Notes

Reaction equation

HRID 2110849 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([CH:13]=O)=[CH:7]2.CO.O1CC[CH2:19][CH2:18]1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C(OCC)(=O)C.[C].[Pd]>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([CH2:13][CH2:18][CH3:19])=[CH:7]2

Participants

8

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 189681295-Fluoro-1H-indole-2-carbaldehyde

Product 1

HCID 23159943HCID 23159943, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 73727Phosphonium, ethyltriphenyl-, bromide (1:1)CatalystHCID 178418390HCID 178418390, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of ethyltriphenylphosphonium bromide (0.86 g, 2.30 mmol) in tetrahydrofuran (20 mL) was added sodium hydride (60% in oil, 80 mg, 1.99 mmol) with stirring at room temperature, and the mixture was stirred at the same temperature for 20 min. To the solution was added 5-fluoro-1H-indole-2-carbaldehyde (0.25 g, 1.53 mmol) synthesized according to the method described in WO99/09025, and the mixture was stirred at 70° C. for 3 hr. After cooling, the reaction mixture was diluted with ethyl acetate, and the mixture washed with water and saturated brine, dried, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=4/1) to give a beige powder. A mixture of the obtained powder, 10% palladium-carbon (50% water-containing product, 0.1 g) and methanol (10 mL) was stirred under a hydrogen atmosphere for 3 hr. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/1-hexane/ethyl acetate=4/1) to give the title compound (0.18 g, yield 65%) as a colorless oil. MS (ESI+): 178 (M+H).

Workup

  1. stirringthe mixture was stirred at the same temperature for 20 min
  2. customsynthesized
  3. stirringwas stirred at 70° C. for 3 hr
  4. temperatureAfter cooling
  5. washthe mixture washed with water and saturated brine
  6. customdried
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=4/1)
  9. customto give a beige powder
  10. stirringwas stirred under a hydrogen atmosphere for 3 hr
  11. filtrationThe catalyst was filtered off
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/1-hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-698b266cf6bd4542a097438de78b3003
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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