Citric Acid → 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate

HRID 2357482Notes

Reaction equation

HRID 2357482 reaction equation
[CH3:1][N:2]([CH3:36])[C:3]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=4)[NH:21][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH2:5][CH2:4]1.C(O)C.[C:40]([OH:52])(=[O:51])[CH2:41][C:42]([CH2:47][C:48]([OH:50])=[O:49])([C:44]([OH:46])=[O:45])[OH:43]>C(Cl)Cl>[C:40]([OH:52])(=[O:51])[CH2:41][C:42]([CH2:47][C:48]([OH:50])=[O:49])([C:44]([OH:46])=[O:45])[OH:43].[CH3:36][N:2]([CH3:1])[C:3]1([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:11]([N:13]2[CH2:14][CH2:15][CH:16]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:28][CH3:29])[CH:26]=4)[NH:21][CH:20]=3)[CH2:17][CH2:18]2)=[O:12])[CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 311Citric AcidHCID 702EthanolHCID 10484698HCID 10484698, compound

Product 1

HCID 104846974-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (197 mg, 0.403 mmole) was dissolved in abs. ethanol (3 ml) and DCM (5 ml). Citric acid (78.3 mg, 0.407 mmole) was added in one portion at ca. 40° C. while stirring. The reaction mixture was stirred for 2 hours at RT. During this time no precipitate formed. The solvents were distilled off down to a volume of 2 ml. Diethyl ether (30 ml) was added to the residue. The suspension was stirred for 20 hours at RT. The precipitate was filtered off, washed with diethyl ether (3×1.5 ml) and dried in vacuo. The polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide citrate (239 mg, m.p. 139°-143° C., 87%, Example 46) was a colourless solid.

Workup

  1. stirringThe reaction mixture was stirred for 2 hours at RT
  2. customDuring this time no precipitate formed
  3. distillationThe solvents were distilled off down to a volume of 2 ml
  4. additionDiethyl ether (30 ml) was added to the residue
  5. stirringThe suspension was stirred for 20 hours at RT
  6. filtrationThe precipitate was filtered off
  7. washwashed with diethyl ether (3×1.5 ml)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-f72c4115fe1d4ae4a51dc23e4423c1cf
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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