Hydrochloric Acid → Almotriptan

HRID 864954Notes

Reaction equation

HRID 864954 reaction equation
C([C:4]1[NH:5][C:6]2[C:11]([C:12]=1[CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])=[CH:10][C:9]([CH2:18][S:19]([N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)(=[O:21])=[O:20])=[CH:8][CH:7]=2)(O)=O.Cl.C(OCC)(=O)C>N1C2C(=CC=CC=2)C=CC=1>[CH3:17][N:15]([CH3:16])[CH2:14][CH2:13][C:12]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:18][S:19]([N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)(=[O:21])=[O:20])[CH:10]=2)[NH:5][CH:4]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 194174753-[2-(Dimethylamino)ethyl]-5-[(1-pyrrolidinylsulfonyl)methyl]-1H-indole-2-carboxylic acid

Product 1

HCID 123606AlmotriptanYield 92%

Reagents, catalysts & solvents 1

HCID 7047QuinolineSolvent

Conditions

Temperature
190 °C

Procedure

To a solution of previously dried 1-[[2-carboxy-3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]pyrrolidine (1.6 g; 0.0442 moles) in anhydrous quinoline (75 ml) and under atmosphere of nitrogen, cuprous oxide (160 mg; 0.0011 moles) was added. The reaction mixture was heated to 190° C. for 15 minutes, stirred to room temperature, poured into a mixture of 1N hydrochloric acid (150 ml) and ethyl acetate (50 ml), shaken and decanted. The aqueous solution was washed several times with ethyl acetate, then solid sodium bicarbonate was added until pH=7.8, and washed with n-hexane to eliminate the quinoline. The aqueous solution was made alkaline with solid potassium carbonate and extracted with ethyl acetate. The organic solution was dried (Na2SO4), the solvent removed under reduced pressure when a dark oil was obtained (1.3 g; yield 92%). This product was purified by column chromatography with silica gel and methylene chloride:ethanol:ammonium hydroxide (60:8:1) as eluent and a white foam (0.8 g) of 1-[[3-(2-dimethylaminoethyl)-5-indolyl]methanesulphonyl]pyrrolidine was obtained.

Workup

  1. stirringshaken
  2. customdecanted
  3. washThe aqueous solution was washed several times with ethyl acetate
  4. additionsolid sodium bicarbonate was added until pH=7.8
  5. washwashed with n-hexane
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic solution was dried (Na2SO4)
  8. customthe solvent removed under reduced pressure when a dark oil
  9. customwas obtained (1.3 g; yield 92%)
  10. customThis product was purified by column chromatography with silica gel and methylene chloride:ethanol:ammonium hydroxide (60:8:1) as eluent

Sources & evidence

ORD record
ord-eeda2a76b0034670a0d9104eec0f247f
Source dataset
uspto-grants-1996_10
Patent number
US05565447

Reaction notes

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