Piperidine, 3,4-didehydro-2,2,6,6-tetramethyl- → HCID 70364728, compound

HRID 728552Notes

Reaction equation

HRID 728552 reaction equation
CC1(C)CC=CC(C)(C)N1.[C:11]1(=[O:27])[CH2:23][CH2:22][CH:21]2[CH2:24][CH2:25][CH2:26][N:19]3[C:20]2=[C:12]1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=13.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:35]2[C:39]([CH3:40])=[C:38]([CH:41]=O)[N:37]=[CH:36]2)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCCCCC.O1CCCC1.C(O)(=O)C>[CH3:41][C:38]1[NH:37][CH:36]=[N:35][C:39]=1[CH:40]=[C:23]1[CH2:22][CH:21]2[CH2:24][CH2:25][CH2:26][N:19]3[C:20]2=[C:12]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=23)[C:11]1=[O:27]

Participants

8

Reactant 4

HCID 70502Piperidine, 3,4-didehydro-2,2,6,6-tetramethyl-HCID 521998p-Toluenesulfonic acid monohydrateHCID 118243385-methyl-1-trityl-1H-imidazole-4-carbaldehydeHCID 54288891HCID 54288891, compound

Product 1

HCID 70364728HCID 70364728, compoundYield 60.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

6.88 mmol butyllium in hexane (4.3 ml; 1.6M) were added dropwise at -78° C. to a solution of 1.2 ml (6.88 mmol) of 2,2,6,6-tetramethylpyridine in 14 ml of dry tetrahydrofuran. The mixture was then stirred for 30 minutes at 0° C., cooled to -70° C., and added dropwise to a solution of 1-4 g (6.23 mmol) of 2,3,3a,4,5,6-hexahydro-1H-pyrido[3,2,1-jk]carbazol-1-one in 42 ml of dry tetrahydrofuran. The mixture was stirred for 90 minutes under nitrogen at -70° C. A solution of 2.4 g (6.88 mmol) of 1-triphenylmethyl-5-methyl-1H-imidazole-4-carboxaldehyde in 14 ml of dry tetrahydrofuran was then added dropwise to the reaction mixture at -70° C., and the mixture was stirred for 2 hours at -10° C. The mixture was then cooled to -70° C. and 16.8 ml of acetic acid was added dropwise. After the temperature had raised to -10° C., 8.1 g of p-toluenesulfonic acid hydrate were added. This mixture was boiled for 18 hours and evaporated in vacuum. The residue was shaken with methylene chloride and with 2N sodium hydroxide. The organic layer was separated, washed with brine, dried and evaporated. The residue was chromatographed over silicagel using methylene chloride/methanol/ammonia (92.5/7/0.5) as an eluent. 1.2 g (60%) of 2,3,3a,4,5,6-hexahydro-2-[(5-methyl-1H-imidazol-4-yl)-methylene]-1H- pyrido[3,2,1jk]carbazol-1-one were obtained. This product dissolved in 100 ml of ethanol and hydrogenated at room temperature at 1 atmosphere with palladium on carbon as a catalyst. The catalyst was removed by filtration after disappearance of the starting material, the filtrate was evaporated in vacuum, and the residue was purified by flash chromatography over silicagel using methyene chloride/methanol/ammonia (92.5/7/0.5) as an eluent. 0.49 g of the desired compound were obtained after evaporating the desired fractions.

Workup

  1. temperaturecooled to -70° C.
  2. stirringThe mixture was stirred for 90 minutes under nitrogen at -70° C
  3. stirringthe mixture was stirred for 2 hours at -10° C
  4. temperatureThe mixture was then cooled to -70° C.
  5. temperatureAfter the temperature had raised to -10° C.
  6. waitThis mixture was boiled for 18 hours
  7. customevaporated in vacuum
  8. stirringThe residue was shaken with methylene chloride and with 2N sodium hydroxide
  9. customThe organic layer was separated
  10. washwashed with brine
  11. customdried
  12. customevaporated
  13. customThe residue was chromatographed

Sources & evidence

ORD record
ord-f04e41a185ee49bfba18f4640cc118ba
Source dataset
uspto-grants-1991_09
Patent number
US05049563

Reaction notes

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