p-Toluenesulfonic acid → HCID 11484605, compound

HRID 898312Notes

Reaction equation

HRID 898312 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9](=O)[CH2:8][CH2:7][CH2:6][C:5]2=1.[NH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:8][CH2:7][CH2:6][C:5]2=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6115AnilineHCID 7085296-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-oneHCID 4311764Sodium borohydride

Product 1

HCID 11484605HCID 11484605, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one (500 mg, 1.9 mmol), aniline (350 mg, 3.8 mmol) and p-toluenesulfonic acid (catalytic) in toluene (15 mL) was heated at reflux for 16 h with a Dean-Stark trap in place. The reaction was cooled, concentrated, and the imine was purified by flash column chromatography on silica (gradient of 5% to 50% ethyl acetate/hexanes). The imine was dissolved in methanol (10 mL) and sodium borohydride (140 mg, 3.8 mmol) was added portionwise. The reaction was stirred for 30 min and quenched with water, concentrated, and diluted with ethyl actetate. The organic phase was separated, absorbed onto diatomaceous earth and purified by flash column chromatography on silica (gradient of 2% to 20% ethyl acetate/hexanes) to provide 6-bromo-N-phenyl-2,3,4,9-tetrahydro-1H-carbazol-1-amine as a brown oil. 1H-NMR (DMSO-d6): δ 8.04 (s, 1H), 7.61 (s, 1H), 7.25-7.21 (m, 4H), 6.80-6.72 (m, 3H), 4.84-4.78 (m, 1H), 3.86-3.82 (m, 1H), 2.27-2.21 (m, 2H), 2.08-2.00 (m, 1H), 1.89-1.78 (m, 3H). The oil was dissolved in diethyl ether and HCl (1.0 M in diethyl ether) was added. The resulting precipitate was collected by filtration to provide 6-bromo-N-phenyl-2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride (352 mg, 51%) as a yellow solid. 1H-NMR (DMSO-d6): δ 11.12 (s, 1H), 7.58 (s, 1H), 7.26 (d, 1H), 7.15-7.13 (m, 3H), 6.88-6.78 (m, 2H), 6.72-6.64 (m, 1H), 4.82-4.79 (m, 1H), 2.69-2.45 (m, 2H), 1.96-1.90 (m, 2H), 1.83-1.73 (m, 2H); MS m/z (M−1) 339, 341.

Workup

  1. temperatureat reflux for 16 h with a Dean-Stark trap in place
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. customthe imine was purified by flash column chromatography on silica (gradient of 5% to 50% ethyl acetate/hexanes)
  5. dissolutionThe imine was dissolved in methanol (10 mL)
  6. customquenched with water
  7. concentrationconcentrated
  8. additiondiluted with ethyl actetate
  9. customThe organic phase was separated
  10. customabsorbed onto diatomaceous earth
  11. custompurified by flash column chromatography on silica (gradient of 2% to 20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f2180f217f0943bb847d9af2d0b4f7ea
Source dataset
uspto-grants-2008_04
Patent number
US07351733B2

Reaction notes

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