Hydrochloric Acid → Ammonium Hydroxide

HRID 593513Notes

Reaction equation

HRID 593513 reaction equation
C[O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=3)[C:13]([CH3:21])=[C:12]2[C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[CH:6][CH:5]=1.[OH-].[Na+].Cl>CO>[NH4+:11].[OH-:2].[Cl:20][C:16]1[CH:15]=[C:14]2[C:19](=[CH:18][CH:17]=1)[N:11]([CH2:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:28])=[O:2])=[CH:5][CH:6]=1)[C:12]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)=[C:13]2[CH3:21]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 445541384-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid methyl ester

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 133620894-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(5-Chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid methyl ester (Example 11, 200 mg, 0.51 mmol) in methanol (5 mL) is added to 5M aqueous NaOH (1 mL, 5 mmol) and the mixture is stirred at room temperature for 5 h. Concentrated HCl (4.4 mL) is added to neutralize the reaction mixture and the solvents are removed in vacuo. The residue is redissolved in methanol and purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% NH4OH in acetonitrile gradient to afford 4-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid. 1H NMR (400 MHz, MeOD) δ ppm 2.25 (s, 3H), 5.34 (s, 2H), 6.82 (d, J=8.1 Hz, 2H), 7.15 (dd, J=8.6, 2.0 Hz, 1H), 7.31 (d, J=8.6 Hz, 1H), 7.50 (dd, J=7.7, 4.9 Hz, 1H), 7.61 (d, J=2.0 Hz, 1H), 7.78-7.80 (m, 1H), 7.81 (d, J=8.1 Hz, 2H), 8.50 (s, 1H), 8.56 (br. s, 1H). HRMS (ESI) m/z 377.1072 [(M+H)+ Calcd for C22H18ClN2O2: 377.1057].

Workup

  1. customthe solvents are removed in vacuo
  2. dissolutionThe residue is redissolved in methanol
  3. custompurified by reverse phase HPLC with Xbridge Shield RP18 column

Sources & evidence

ORD record
ord-3b248e14af534cd6af80d7e43333ee1d
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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