Acetic Acid → Ammonium Hydroxide

HRID 1630786Notes

Reaction equation

HRID 1630786 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:13]=C([CH:17]=[CH:18][CH:19]=1)C#N)[C:6]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[C:5]2[CH3:26].Cl.[C:28]([OH:31])(=[O:30])[CH3:29]>>[NH4+:7].[OH-:30].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:13]=[C:29]([CH:17]=[CH:18][CH:19]=1)[C:28]([OH:31])=[O:30])[C:6]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)=[C:5]2[CH3:26]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 582157933-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzonitrile

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 445543123-(5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid

Procedure

3-(5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzonitrile (Example 14, 200 mg, 0.56 mmol) in acetic acid (3 mL) is added to a 20% HCl aqueous solution (3 mL). The reaction mixture is refluxed for 3 days. The volatiles are removed in vacuo and the residue is redissolved in methanol and purified by reverse phase HPLC with Xbridge Shield RP18 and a gradient of 0.1% NH4OH in acetonitrile to give 3-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl)-benzoic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.21 (s, 3H), 5.36 (s, 2H), 6.83 (d, J=7.1 Hz, 1H), 7.13-7.23 (m, 2H), 7.43-7.52 (m, 3H), 7.64-7.70 (m, 2H), 7.74-7.81 (m, 1H), 8.55 (s, 1H), 8.61-8.62 (m, 1H). HRMS (ESI) m/z 377.1058 [(M+H)+ Calcd for C22H18ClN2O2: 377.1057].

Workup

  1. temperatureThe reaction mixture is refluxed for 3 days
  2. customThe volatiles are removed in vacuo
  3. dissolutionthe residue is redissolved in methanol
  4. custompurified by reverse phase HPLC with Xbridge Shield RP18

Sources & evidence

ORD record
ord-ed834ab03e3b433295fddd612ececfaa
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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