Oxalic Acid → 1-(4-Indolyloxy)-4-(4-(2-naphthyl)piperidin-1-yl)butane ethanedioate

HRID 1599588Notes

Reaction equation

HRID 1599588 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+].[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40]>C(#N)C.C(OCC)(=O)C>[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40].[NH:11]1[C:12]2[C:8](=[C:7]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:29]3[CH2:30][CH2:31][CH:26]([C:17]4[CH:18]=[CH:19][C:20]5[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=5)[CH:16]=4)[CH2:27][CH2:28]3)[CH:15]=[CH:14][CH:13]=2)[CH:9]=[CH:10]1

Participants

7

Reactant 4

HCID 971Oxalic AcidHCID 11430Potassium CarbonateHCID 115721114-(4-chlorobutoxy)-1H-indoleHCID 220292644-(Naphthalen-2-yl)piperidine

Product 1

HCID 867500031-(4-Indolyloxy)-4-(4-(2-naphthyl)piperidin-1-yl)butane ethanedioate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 1-chloro-4-(4-indolyloxy)butane (prepared from 4-hydroxy-1H-indole and 1-bromo-4-chlorobutane), 4-(2-naphthyl)piperidine and 3 equivalents of potassium carbonate in acetonitrile was heated at reflux for 12 h. The mixture was cooled and diluted with ethyl acetate, and the organic layer was separated and washed with brine. The crude residue was purified by silica gel chromatography (dichloromethane/5% methanol in dichloromethane gradient eluent). The resulting free base was dissolved in ethyl acetate and precipitated with one equivalent of oxalic acid in ethyl acetate, to give the title compound in 48% overall yield as a tan solid. mp 113°-115° C. FDMS m/e=398 (M+ of free base).

Workup

  1. temperatureat reflux for 12 h
  2. temperatureThe mixture was cooled
  3. customthe organic layer was separated
  4. washwashed with brine
  5. customThe crude residue was purified by silica gel chromatography (dichloromethane/5% methanol in dichloromethane gradient eluent)
  6. dissolutionThe resulting free base was dissolved in ethyl acetate

Sources & evidence

ORD record
ord-c73dc2c6c5f74be0be80216b2d9a7340
Source dataset
uspto-grants-1998_04
Patent number
US05741789

Reaction notes

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