Hydrochloric Acid → 3-[2-(4-Dimethylamino-4-phenyl-cyclohexylamino)-ethyl]-1H-indol-5-ol dihydrochloride

HRID 1179077

Reaction equation

HRID 1179077 reaction equation
[CH:1]1[C:6]([OH:7])=[CH:5][C:4]2[C:8]([CH2:11][CH2:12][NH2:13])=[CH:9][NH:10][C:3]=2[CH:2]=1.[CH3:14][N:15]([CH3:29])[C:16]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:51].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>ClCCCl.C1COCC1.C(O)C.CC(=O)CC.C(O)(=O)C>[ClH:51].[ClH:51].[CH3:14][N:15]([CH3:29])[C:16]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:17][CH2:18][CH:19]([NH:13][CH2:12][CH2:11][C:8]2[C:4]3[C:3](=[CH:2][CH:1]=[C:6]([OH:7])[CH:5]=3)[NH:10][CH:9]=2)[CH2:20][CH2:21]1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 5202SerotoninHCID 24436Sodium SulfateHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 114244924-(Dimethylamino)-4-phenylcyclohexan-1-one

Product 1

HCID 693382623-[2-(4-Dimethylamino-4-phenyl-cyclohexylamino)-ethyl]-1H-indol-5-ol dihydrochloride

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 21493386Dce thfSolventHCID 225585302-Butanone ethanolSolvent

Procedure

Serotonin (405 mg) was dissolved in 1,2-dichloroethane/THF (5 ml/20 ml), and 4-dimethylamino-4-phenylcyclohexanone (500 mg), glacial acetic acid (131 μl) and red-hot sodium sulfate (2 g) were added thereto. After one hour's stirring at RT, sodium triacetoxyborohydride (759 mg) was added and stirring was carried out for a further two days. For working up, the mixture was concentrated, the residue was suspended in diethyl ether (15 ml), water (10 ml) and 2M HCl (1 ml), further diethyl ether (20 ml) was added, and the organic phase was coarsely separated off. The aqueous phase was first brought to pH 9 with 1M NaOH and extracted with ethyl acetate (3×5 ml), then adjusted to pH 11 and again extracted with ethyl acetate (5×10 ml). The organic extracts were dried and concentrated and the residue was purified by flash chromatography (eluant: MeOH/NEt3 99.5:0.5). 267 mg of the nonpolar diastereomer (m.p. 90-100° C.) were isolated and, dissolved in ethanol/2-butanone (3 ml/15 ml), were converted with 3.3M ethanolic HCl (642 μl) into the corresponding dihydrochloride (white solid; 304 mg; m.p. 215-217° C.).

Workup

  1. stirringstirring
  2. waitwas carried out for a further two days
  3. concentrationthe mixture was concentrated
  4. additionwater (10 ml) and 2M HCl (1 ml), further diethyl ether (20 ml) was added
  5. customthe organic phase was coarsely separated off
  6. extractionextracted with ethyl acetate (3×5 ml)
  7. extractionagain extracted with ethyl acetate (5×10 ml)
  8. customThe organic extracts were dried
  9. concentrationconcentrated
  10. customthe residue was purified by flash chromatography (eluant: MeOH/NEt3 99.5:0.5)
  11. custom267 mg of the nonpolar diastereomer (m.p. 90-100° C.) were isolated

Sources & evidence

ORD record
ord-08155d8224974509a2b5b6bab7a549eb
Source dataset
uspto-grants-2007_10
Patent number
US07276518B2

Linked notes

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