Ammonia → ethyl 1-[2-(4-methylphenylsulfonyl)aminoethyl]-4-methyl-1H-indole-2-carboxylate

HRID 1600645Notes

Reaction equation

HRID 1600645 reaction equation
C(OC([NH:8][CH2:9][CH2:10][N:11]1[C:19]2[C:14](=[C:15]([CH3:20])[CH:16]=[CH:17][CH:18]=2)[CH:13]=[C:12]1[C:21]([O:23][CH2:24][CH3:25])=[O:22])=O)(C)(C)C.FC(F)(F)C(O)=O.N.[C:34]1([CH3:44])[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>ClCCl>[CH3:44][C:34]1[CH:39]=[CH:38][C:37]([S:40]([NH:8][CH2:9][CH2:10][N:11]2[C:19]3[C:14](=[C:15]([CH3:20])[CH:16]=[CH:17][CH:18]=3)[CH:13]=[C:12]2[C:21]([O:23][CH2:24][CH3:25])=[O:22])(=[O:42])=[O:41])=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 73974-Toluenesulfonyl chlorideHCID 21714333ethyl 1-(2-tert-butoxycarbonylaminoethyl)-4-methyl-1H-indole-2-carboxylate

Product 1

HCID 21714328ethyl 1-[2-(4-methylphenylsulfonyl)aminoethyl]-4-methyl-1H-indole-2-carboxylateYield 87.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of ethyl 1-(2-tert-butoxycarbonylaminoethyl)-4-methyl-1H-indole-2-carboxylate (27.2 g, 78.5 mmol), trifluoroacetic acid (75 ml) and dichloromethane (250 ml) was stirred at 0° C. for 3 hours, slowly poured into cold aqueous ammonia, and then extracted twice with ethyl acetate. The extract solution was washed with a 5% aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, after which the residue was dissolved in pyridine (150 ml) and the resulting solution was cooled to 5° C. p-Toluenesulfonyl chloride (22.4 g, 118 mmol) was added to the cooled solution in small portions and the resulting mixture was stirred at 5° C. for 3 hours and then allowed to stand overnight at room temperature. The reaction mixture was poured into ice water and extracted twice with ethyl acetate, and the extract solution was washed successively with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and a 5% aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was purified by a silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/9) to obtain 27.6 g of ethyl 1-[2-(4-methylphenylsulfonyl)aminoethyl]-4-methyl-1H-indole-2-carboxylate.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe extract solution was washed with a 5% aqueous sodium chloride solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. dissolutionafter which the residue was dissolved in pyridine (150 ml)
  6. additionwas added to the cooled solution in small portions
  7. stirringthe resulting mixture was stirred at 5° C. for 3 hours
  8. waitto stand overnight at room temperature
  9. extractionextracted twice with ethyl acetate
  10. washthe extract solution was washed successively with 1N hydrochloric acid
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe resulting residue was purified by a silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/9)

Sources & evidence

ORD record
ord-34394b87a02444059d8aa51c3419f53b
Source dataset
uspto-grants-1999_11
Patent number
US05977100

Reaction notes

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