N-Phenyl-2-benzyloxyethylamine → [9-(2-Benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazol-4-yl]-piperidin-1-yl-methanone

HRID 1753928Notes

Reaction equation

HRID 1753928 reaction equation
Br[CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:9])[C:3]1=O.[CH2:17]([O:24][CH2:25][CH2:26][NH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CC(O)C.[Cl-].[Zn+2].[Cl-]>[CH2:17]([O:24][CH2:25][CH2:26][N:27]1[C:2]2[CH2:7][CH2:6][CH2:5][CH:4]([C:8]([N:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)=[O:9])[C:3]=2[C:33]2[C:28]1=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 2

HCID 571665N-Phenyl-2-benzyloxyethylamineHCID 666798302-Bromo-6-(piperidine-1-carbonyl)-cyclohexanone

Product 1

HCID 66680375[9-(2-Benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazol-4-yl]-piperidin-1-yl-methanoneYield 27.7%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 2-bromo-6-(piperidine-1-carbonyl)-cyclohexanone (20) (1.5 g, 5.2 mmol) and (2-benzyloxy-ethyl)-phenyl-amine (21) (3.2 g, 10.4 mmol) was stirred under N2 at 50° C. for 3 h and the reaction turned brown. The resulting mixture was dissolved in propan-2-ol (5 mL) and dry zinc chloride (2.13 g, 15.6 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and washed with 2 N HCl (30 mL), water (2×30 mL) and aqueous potassium carbonate solution (2×30 mL) then dried and concentrated in vacuo. The crude material was purified by SCX cartridge and then silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (30-100% B, 12 g, 41 CV, 30 mL/min) to afford 600 mg (27%) of [9-(2-benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazol-4-yl]-piperidin-1-yl-methanone (22) as an oil. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 21.5, 21.7, 24.5, 25.7, 26.3, 273, 37.7, 42.8, 43.1, 46.7, 60.2, 68.7, 73.1, 108.2, 108.7, 117.8, 118.9, 120.5, 126.4, 127.3, 127.4, 128.1, 136.2, 137.8, 172.9.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux under N2 for 16 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washwashed with 2 N HCl (30 mL), water (2×30 mL) and aqueous potassium carbonate solution (2×30 mL)
  6. customthen dried
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by SCX cartridge
  9. washsilica gel chromatography eluting with petrol (A) and ethyl acetate (B) (30-100% B, 12 g, 41 CV, 30 mL/min)

Sources & evidence

ORD record
ord-1f63ebf93ea34ec8aaa13ce6aed1cb6d
Source dataset
uspto-grants-2015_10
Patent number
US09168317B2

Reaction notes

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