Benzenesulfonate → [4-(5-aminomethyl-2-fluorophenyl)piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone benzenesulfonate

HRID 1513369Notes

Reaction equation

HRID 1513369 reaction equation
O.[C:2]1([S:8]([OH:11])(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([F:47])=[C:18]([CH:20]2[CH2:25][CH2:24][N:23]([C:26]([C:28]3[C:36]4[C:31](=[C:32]([F:42])[CH:33]=[CH:34][C:35]=4[O:37][C:38]([F:41])([F:40])[F:39])[N:30]([CH2:43][CH2:44][O:45][CH3:46])[CH:29]=3)=[O:27])[CH2:22][CH2:21]2)[CH:19]=1.C1(S([O-])(=O)=O)C=CC=CC=1>C(#N)C>[C:2]1([S:8]([OH:11])(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([F:47])=[C:18]([CH:20]2[CH2:25][CH2:24][N:23]([C:26]([C:28]3[C:36]4[C:31](=[C:32]([F:42])[CH:33]=[CH:34][C:35]=4[O:37][C:38]([F:41])([F:39])[F:40])[N:30]([CH2:43][CH2:44][O:45][CH3:46])[CH:29]=3)=[O:27])[CH2:22][CH2:21]2)[CH:19]=1

Participants

5

Reactant 3

HCID 91526BenzenesulfonateHCID 15619088Hydroxybenzenesulfonic acidHCID 44631896[4-(5-aminomethyl-2-fluorophenyl)piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone

Product 1

HCID 86656587[4-(5-aminomethyl-2-fluorophenyl)piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone benzenesulfonate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of benzenesulfonic acid monohydrate (698 mg, 3.84 mmol) in acetonitrile (12 mL) was added drop-wise to a stirred suspension of [4-(5-aminomethyl-2-fluorophenyl)piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone (2.0 g, 3.91 mmol) in acetonitrile (5 mL). The benzenesulfonate salt began to crystallize from the mixture as the last of the free base dissolved. After 2 h, the product was collected by filtration and washed with acetonitrile. The filter cake was allowed to dry overnight. The solids were broken up and dried in a vacuum oven @43-44° C. at 6.8-7.3″ of Hg with a nitrogen bleed for 7.5 h to give [4-(5-aminomethyl-2-fluorophenyl)piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone benzenesulfonate as a colorless solid: 2.27 g 1 (86.7%), mp=215-218° C. Anal. Calculated. For C25H26F5N3O3.C6H6O3S: C, 55.60; H, 4.82; N, 6.27. Found: C, 55.65; H, 4.65; N, 6.27. Karl Fischer: <0.10. Infrared spectral features (cm-1): 1587, 1545, 1445, 1210, 1167, 1125, 1036, 1018.

Workup

  1. customto crystallize from the mixture as the last of the free base
  2. dissolutiondissolved
  3. filtrationthe product was collected by filtration
  4. washwashed with acetonitrile
  5. customto dry overnight
  6. customdried in a vacuum oven @43-44° C. at 6.8-7.3″ of Hg with a nitrogen
  7. waitbleed for 7.5 h

Sources & evidence

ORD record
ord-3cc7c82846914f66a1450daaf7ecdafd
Source dataset
uspto-grants-2012_07
Patent number
US08217178B2

Reaction notes

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