Hydrochloric Acid → 5-(biphenyl-4-yl)-6-chloro-1H-indole-3-carboxylic acid

HRID 1054670Notes

Reaction equation

HRID 1054670 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:15]=2[Cl:16])[NH:12][CH:11]=[C:10]3[C:17]([O:19]C)=[O:18])=[CH:3][CH:2]=1.[OH-].[Na+].Cl>CO>[C:1]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][C:15]=2[Cl:16])[NH:12][CH:11]=[C:10]3[C:17]([OH:19])=[O:18])=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86698673methyl 5-(biphenyl-4-yl)-6-chloro-1H-indole-3-carboxylate

Product 1

HCID 866986745-(biphenyl-4-yl)-6-chloro-1H-indole-3-carboxylic acidYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 5-(biphenyl-4-yl)-6-chloro-1H-indole-3-carboxylate (50 mg, 0.14 mmol) in methanol (1.5 mL) and sodium hydroxide (1 M, 0.50 mmol, 0.50 mL) was stirred at 75° C. for 24 hours. The cooled reaction mixture was neutralized to an acidic pH with 1M HCl and extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Methylene chloride was then added and solid precipitated. The slurry was stirred for 30 minutes then filtered and washed with methylene chloride and a small amount of ethyl acetate. The solids were dried in vacuo to provide the desired product as a tan solid (17 mg, 35% yield). MS (ES+) 348.1 (M+H)+. 1H NMR (500 MHz, DMSO-d6) δ 12.14 (br. s., 1H), 11.98 (br. s., 1H), 8.10 (d, J=2.93 Hz, 1H), 8.01 (s, 1H), 7.75 (t, J=8.42 Hz, 4H), 7.67 (s, 1H), 7.54 (d, J=8.05 Hz, 2H), 7.50 (t, J=7.56 Hz, 2H), 7.32-7.45 (m, 1H).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted twice with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionMethylene chloride was then added
  7. customsolid precipitated
  8. filtrationthen filtered
  9. washwashed with methylene chloride
  10. customThe solids were dried in vacuo

Sources & evidence

ORD record
ord-0fe5504064934529a666cef7b712232b
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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