Hydrochloric Acid → 6-chloro-5-{4-[3-(morpholin-4-yl)propoxy]phenyl}-1H-indole-3-carboxylic acid

HRID 338324Notes

Reaction equation

HRID 338324 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:17][CH:16]=1.[OH-].[Na+].Cl>CO.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([O:21][CH2:22][CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86698670methyl 6-chloro-5-{4-[3-(morpholin-4-yl)propoxy]phenyl}-1H-indole-3-carboxylate

Product 1

HCID 717659516-chloro-5-{4-[3-(morpholin-4-yl)propoxy]phenyl}-1H-indole-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 6-chloro-5-{4-[3-(morpholin-4-yl)propoxy]phenyl}-1H-indole-3-carboxylate (24 mg, 0.056 mmol) in methanol (0.5 mL) and 1M sodium hydroxide (0.17 mL, 0.17 mmol) was heated at 75° C. for 24 hours. The reaction was acidified with 1M HCl to pH=2 then diluted with ethyl acetate. The layers were separated and the aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified using reverse-phase chromatography to give the title compound as the formic acid salt. MS (ES+) 415.129 (M+H)±Retention time: 2.2 min; Waters Atlantis dC18 5 μm 4.6×50 mm, 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. (0.05% TFA) Flow: 2.0 mL/min.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was back-extracted twice with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-42115fc289d94d1684a38830e977ad7c
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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