Pyridine → 1-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-(2-pyrrolidon-1-yl)methylindole

HRID 1790512Notes

Reaction equation

HRID 1790512 reaction equation
[F:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([CH2:23][NH2:24])[CH:21]=4)[CH:16]=[CH:15]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(OCC(Cl)=O)(=O)C.N1C=CC=CC=1.[O:41]1[CH2:45][CH2:44][CH2:43][CH2:42]1>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH:11]([N:14]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([CH2:23][N:24]5[CH2:45][CH2:44][CH2:43][C:42]5=[O:41])[CH:21]=4)[CH:16]=[CH:15]3)[CH2:12][CH2:13]2)=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 8028TetrahydrofuranHCID 26297Acetoxyacetyl chlorideHCID 22038390HCID 22038390, compound

Product 1

HCID 220379311-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-(2-pyrrolidon-1-yl)methylindoleYield 80%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-aminomethylindole (150 mg) obtained in Example 322-3), acetoxyacetyl chloride (64 mg), pyridine (3 ml) and tetrahydrofuran (5 ml) was stirred under ice cooling for 30 min. Then ice water and ethyl acetate were added to the reaction mixtures. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the resulting residue were added methanol (10 ml) and potassium carbonate (100 mg) followed by stirring for 30 min. Then ice water and ethyl acetate were added to the reaction mixtures. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/ethanol system) to give the title compound (140 mg) as white scales (yield: 80%).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo the resulting residue were added methanol (10 ml) and potassium carbonate (100 mg)
  6. stirringby stirring for 30 min
  7. additionThen ice water and ethyl acetate were added to the reaction mixtures
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/ethanol system)

Sources & evidence

ORD record
ord-f6008e2deae94d1d9608c4cff099a8cd
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

Loading…