Acetic Acid → 1-benzyl-N'-(1H-indol-3-ylmethyl)-N,N-dimethylcyclohexane-1,4-diamine dihydrochloride

HRID 1179043

Reaction equation

HRID 1179043 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][NH2:11])=[CH:2]1.[CH2:12]([C:19]1([N:26]([CH3:28])[CH3:27])[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:47]>ClCCCl.CC(=O)CC.C(O)C.O>[ClH:47].[ClH:47].[CH2:12]([C:19]1([N:26]([CH3:27])[CH3:28])[CH2:24][CH2:23][CH:22]([NH:11][CH2:10][C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][CH:2]=2)[CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 4721071H-Indol-3-YlmethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 204534784-Benzyl-4-(dimethylamino)cyclohexanone

Product 1

HCID 693372961-benzyl-N'-(1H-indol-3-ylmethyl)-N,N-dimethylcyclohexane-1,4-diamine dihydrochloride

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 225585302-Butanone ethanolSolvent

Procedure

292 mg C-(1H-indol-3-yl)-methylamine were partly dissolved in dry 1,2-dichloroethane (10 ml) under argon. After addition of 463 mg 4-benzyl-4-dimethylamino-cyclohexanone (see example 3), glacial acetic acid (4 mmol) and sodium triacetoxyborohydride (550 mg), the suspension was stirred for 72 hours at room temperature. For working up, water (10 ml) was added to the reaction mixture. The organic phase was separated off and the aqueous phase was extracted twice with ether and then rendered strongly alkaline with sodium hydroxide solution. The mixture was extracted again with ethyl acetate (4×10 ml). A pale precipitate precipitated out of the combined ethyl acetate phases even during the processing. After cooling, this was filtered off with suction, washed twice with cold ethyl acetate and dried. The product obtained in this way (235 mg) was white and solid (m.p. 194-198° C.). 217 mg were dissolved hot in 2-butanone/ethanol (30+10 ml), and saturated ethanolic hydrochloric acid (1.5 ml; 1.85 M) was added at RT, while stirring. After two hours, no precipitate had yet precipitated out. Even after reducing the amount of solvent and cooling, no hydrochloride precipitated out. The mixture was therefore evaporated to dryness at 40° C. in vacuo and excess HCl was driven off. 260 mg 1-benzyl-N′-(1H-indol-3-ylmethyl)-N,N-dimethylcyclohexane-1,4-diamine dihydrochloride were obtained as the residue as a pale pink-colored solid of m.p. 170-174° C.

Workup

  1. customThe organic phase was separated off
  2. extractionthe aqueous phase was extracted twice with ether
  3. extractionThe mixture was extracted again with ethyl acetate (4×10 ml)
  4. customA pale precipitate precipitated out of the combined ethyl acetate phases even during the processing
  5. temperatureAfter cooling
  6. filtrationthis was filtered off with suction
  7. washwashed twice with cold ethyl acetate
  8. customdried
  9. customThe product obtained in this way (235 mg)
  10. stirringwhile stirring
  11. waitAfter two hours
  12. customno precipitate had yet precipitated out
  13. temperaturecooling
  14. customno hydrochloride precipitated out
  15. customThe mixture was therefore evaporated to dryness at 40° C. in vacuo and excess HCl

Sources & evidence

ORD record
ord-57c1bb2d8e164248ab7a566df73b8d85
Source dataset
uspto-grants-2007_10
Patent number
US07276518B2

Linked notes

Loading…