Oxalic Acid → 10-ethyl-8,9-dihydro-7-[(hydroxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one

HRID 847517Notes

Reaction equation

HRID 847517 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]2[C:24](=[O:28])[CH2:25][CH2:26][CH2:27][C:16]=12)[CH3:14].[CH3:29][C:30]1[N:34]([C:35]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:33]=[N:32][C:31]=1[CH:54]=[O:55].C(O)(=O)C(O)=O>O1CCCC1.CCCCCC.O>[CH2:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]2[C:24](=[O:28])[CH:25]([CH:54]([OH:55])[C:31]3[N:32]=[CH:33][N:34]([C:35]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:30]=3[CH3:29])[CH2:26][CH2:27][C:16]=12)[CH3:14]

Participants

9

Reactant 5

HCID 971Oxalic AcidHCID 7912DiisopropylamineHCID 118243385-methyl-1-trityl-1H-imidazole-4-carbaldehydeHCID 1505194510-ethyl-8,9-dihydropyrido[1,2-a]indol-6(7H)-oneHCID 178418339Butyllithium

Product 1

HCID 1005366010-ethyl-8,9-dihydro-7-[(hydroxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-oneYield 80.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of diisopropylamine (1.85 g) in tetrahydrofuran (15 ml) at -70° C. under a nitrogen atmosphere was added 1.49 M butyllithium in hexane (11.5 ml). After being stirred at the same temperature for 35 minutes, the mixture was treated with a solution of 10-ethyl-8,9-dihydropyrido[1,2-a]indol-6(7H)-one (3.2 g) in tetrahydrofuran (20 ml) over 5 minutes. The mixture was stirred at -70° C. for 40 minutes, and a solution of 5-methyl-1-trityl-1H-imidazol-4-carbaldehyde (5.81 g) in tetrahydrofuran (65 ml) was added dropwise over 30 minutes. After the mixture was stirred at -70° C. for 2 hours and then at room temperature for 1 hour, it was diluted with chilled water, neutralized with aqueous oxalic acid solution, and extracted with methylene chloride three times. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The oil obtained was purified by silica gel column chromatography (1% methanol-chloroform) to give 10-ethyl-8,9-dihydro-7-[(hydroxy)(5-methyl-1-trityl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (6.8 g) as an amorphous powder. The product was a mixture of two diastereoisomers.

Workup

  1. stirringThe mixture was stirred at -70° C. for 40 minutes
  2. stirringAfter the mixture was stirred at -70° C. for 2 hours
  3. waitat room temperature for 1 hour
  4. extractionextracted with methylene chloride three times
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customThe oil obtained
  9. customwas purified by silica gel column chromatography (1% methanol-chloroform)

Sources & evidence

ORD record
ord-5c72b75a142647129a84b3d5520bd4ff
Source dataset
uspto-grants-1992_08
Patent number
US05141945

Reaction notes

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