Triphenylphosphine → HCID 66606356, compound

HRID 662004Notes

Reaction equation

HRID 662004 reaction equation
[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([CH2:15]O)=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1.ClN1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:47][S-:48].[Na+]>C(Cl)Cl.CCOC(C)=O.CS(C)=O>[Br:1][C:2]1[C:14]2[C:13]3[C:8](=[CH:9][C:10]([CH2:15][S:48][CH3:47])=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:5]([C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 4378561Sodium methanethiolateHCID 66606607HCID 66606607, compound

Product 1

HCID 66606356HCID 66606356, compoundYield 38.1%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step 1 A mixture of 4-bromo-7-(hydroxymethyl)-9H-carbazole-1-carboxamide (Example 30-2, 403 mg, 1.263 mmol), N-chlorosuccinimide (219 mg, 1.642 mmol) and triphenylphosphine (431 mg, 1.642 mmol) in DCM (50 mL) was heated at reflux for 1 h. The mixture was cooled to rt, washed with brine, and the aqueous layer was extracted with DCM. The aqueous layer was filtered and the collected precipitate was washed with water. The organic layers and the collected precipitate were combined and the mixture was concentrated under vacuum. The residue was dissolved in THF (20 mL) and DMSO (5 mL) and the solution was treated with sodium thiomethoxide (115 mg, 1.642 mmol). The mixture was stirred at rt for 30 min, diluted with EtOAc, washed twice with water, and the aqueous phase was extracted with EtOAc. The combined organic phases were dried and concentrated. The residue was purified by column chromatography (eluting with EtOAc-hexane) to provide 4-bromo-7-(methylthiomethyl)-9H-carbazole-1-carboxamide as a white solid (168 mg, 38%) used without further purification. 1H NMR (400 MHz, chloroform-d) δ 8.67 (1H, d, J=8.1 Hz), 7.46-7.52 (2H, m), 7.36-7.41 (1H, m), 7.26-7.29 (1H, m), 3.87 (2H, s), 2.03 (3H, s). Mass spectrum m/z 349, 351 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. washwashed with brine
  4. extractionthe aqueous layer was extracted with DCM
  5. filtrationThe aqueous layer was filtered
  6. washthe collected precipitate was washed with water
  7. concentrationthe mixture was concentrated under vacuum
  8. dissolutionThe residue was dissolved in THF (20 mL)
  9. washwashed twice with water
  10. extractionthe aqueous phase was extracted with EtOAc
  11. customThe combined organic phases were dried
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography (eluting with EtOAc-hexane)

Sources & evidence

ORD record
ord-90c59c6ff498430da2e0dbc818afa030
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

Loading…