p-Toluenesulfonic acid → HCID 9795142, compound

HRID 327081Notes

Reaction equation

HRID 327081 reaction equation
[C:1]1(C)C=CC(S(O)(=O)=O)=CC=1.FC(F)(F)C([NH:16][CH2:17][CH:18]1[C:24]2=[CH:25][NH:26][C:27]3[CH:28]=[CH:29][CH:30]=[C:22]([C:23]=32)[C:21](=[O:31])[N:20]([CH2:32][OH:33])[CH2:19]1)=O>CO>[NH2:16][CH2:17][CH:18]1[C:24]2=[CH:25][NH:26][C:27]3[CH:28]=[CH:29][CH:30]=[C:22]([C:23]=32)[C:21](=[O:31])[N:20]([CH2:32][O:33][CH3:1])[CH2:19]1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 19734261HCID 19734261, compound

Product 1

HCID 9795142HCID 9795142, compoundYield 332%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

0.1 g of p-toluenesulfonic acid was added to a solution of 1.5 g of 3-trifluoroacetamidomethyl-5-hydroxymethyl-3,4,5,6-tetrahydro-6-oxo-1H-azepino[5,4,3-cd]indole (see Example 11C for preparation) in 25 ml of methanol, and the solution was heated under reflux for 2 hours. The reaction mixture was then concentrated, and saturated aqueous potassium carbonate solution was added to the residue until a pH of 11 was reached, and the mixture was stirred at room temperature for 4 hours. The treatment with the saturated aqueous potassium carbonate solution eliminated the trifluoroacetyl protective group and neutralized the p-toluenesulfonic acid. To work up the reaction mixture it was subsequently evaporated to dryness, the residue was taken up in methanol, insoluble components were removed by filtration, and the residue on the filter was washed twice more with 30 ml portions of methanol. The combined methanol phases were evaporated and the residue was purified by chromatography under moderately elevated pressure (=low-pressure chromatography under 3 to 6 bar) on silica gel using methanol/25% strength aqueous ammonia solution 97:3 as eluent. The title compound which remained after concentration of the eluate was crystallized from ethanol/ether 9:1. 0.5 g of 3-aminomethyl-5-methoxymethyl-3,4,5,6-tetrahydro-6-oxo-1H-azepino[5,4,3-cd]indole was obtained with a melting point of 160° to 163° C.

Workup

  1. temperaturethe solution was heated
  2. temperatureunder reflux for 2 hours
  3. concentrationThe reaction mixture was then concentrated
  4. additionsaturated aqueous potassium carbonate solution was added to the residue until a pH of 11
  5. customwas subsequently evaporated to dryness
  6. custominsoluble components were removed by filtration
  7. washthe residue on the filter was washed twice more with 30 ml portions of methanol
  8. customThe combined methanol phases were evaporated
  9. customthe residue was purified by chromatography under moderately elevated pressure (=low-pressure chromatography under 3 to 6 bar) on silica gel
  10. customwas crystallized from ethanol/ether 9:1

Sources & evidence

ORD record
ord-cfe447852a30492295b358eb98ef4ea1
Source dataset
uspto-grants-1993_12
Patent number
US05272143

Reaction notes

Loading…