Trimethyl orthoformate → 7-Methoxycarbonylmethyl-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinoline

HRID 1003711Notes

Reaction equation

HRID 1003711 reaction equation
O.O.O.[N+]([O-])([O-])=O.[Tl+3].[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[CH:17]([O:22][CH3:23])([O:20]C)OC.Cl.[C:25]([C:28]1[CH:37]=[C:36]2[C:31]([CH2:32][CH2:33][N:34]([CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:56])[C:44]3[CH:49]=[CH:48][C:47]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)=[CH:46][CH:45]=3)[CH2:35]2)=[CH:30][CH:29]=1)(=O)C>CO.ClCCl>[CH3:23][O:22][C:17]([CH2:25][C:28]1[CH:37]=[C:36]2[C:31]([CH2:32][CH2:33][N:34]([CH2:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:56])[C:44]3[CH:45]=[CH:46][C:47]([C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)=[CH:48][CH:49]=3)[CH2:35]2)=[CH:30][CH:29]=1)=[O:20]

Participants

6

Reactant 3

HCID 9005Trimethyl orthoformateHCID 11270721Nitric acid,thallium(3+) salt, trihydrate (9CI)HCID 1317217547-Acetyl-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinoline, hydrochloride

Product 1

HCID 187970057-Methoxycarbonylmethyl-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinolineYield 30%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of thallium (III) nitrate trihydrate (0.73 g, 1.6 mmol), K10 clay (1.65 g) and trimethyl orthoformate (1.8 ml, 1.6 mmol) in methanol (3 ml) was stirred at room temperature for 15 min. The solvent was evaporated in vacuo and dichloromethane (5 ml) was added to the residue. To this mixture was added a solution of 7-acetyl-2-(4-(4-phenylbenzoylamino)butyl)-1,2,3,4-tetrahydroisoquinoline, hydrochloride (0.50 g, 1.1 mmol) in dichloromethane (15 ml) and the reaction mixture was stirred for 4 h. The suspended solid was removed by filtration and the filtrate was washed with saturated aqueous potassium carbonate (2×30 ml), then brine (30 ml). Drying (Na2SO4) and evaporation in vacuo afforded a yellow gum which was chromatographed on silica using 20-100% ethyl acetate--pentane gradient elution to afford the title compound as an off-white solid (0.15 g, 30%).

Workup

  1. customThe solvent was evaporated in vacuo and dichloromethane (5 ml)
  2. additionwas added to the residue
  3. customThe suspended solid was removed by filtration
  4. washthe filtrate was washed with saturated aqueous potassium carbonate (2×30 ml)
  5. customDrying
  6. custom(Na2SO4) and evaporation in vacuo
  7. customafforded a yellow gum which
  8. customwas chromatographed on silica using 20-100% ethyl acetate
  9. washpentane gradient elution

Sources & evidence

ORD record
ord-541ee847a9484995948dd89a307411f6
Source dataset
uspto-grants-2000_04
Patent number
US06046210

Reaction notes

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