Hydrochloric Acid → 6-Fluoro-5-(4-methoxy-phenyl)-1H-indole-3-carboxylic acid

HRID 1054656Notes

Reaction equation

HRID 1054656 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1.O.[OH:22]P([O-])(O)=O.[Na+].OO.Cl([O-])=O.[Na+].S([O-])([O-])=O.[Na+].[Na+].Cl>CC#N.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:22])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium Chlorite2×HCID 866986596-Fluoro-5-(4-methoxy-phenyl)-1H-indole-3-carbaldehyde

Product 1

HCID 866986606-Fluoro-5-(4-methoxy-phenyl)-1H-indole-3-carboxylic acidYield 27.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 6-fluoro-5-(4-methoxy-phenyl)-1H-indole-3-carbaldehyde (106.0 mg, 0.39 mmol) in MeCN (5 mL) and water (3 mL) was added sodium phosphate monobasic hydrate (12.3 mg, 0.087 mmol), 25% hydrogen peroxide (56.3 mg, 0.41 mmol) and sodium chlorite (44.5 mg, 0.39 mmol). The reaction mixture was stirred for one hour at room temperature and additional MeCN (5 mL) and sodium chlorite (44.5 mg, 0.39 mmol) were added. The reaction mixture was heated to 50° C. for one hour, cooled to room temperature and stirred for another 16 hours. The reaction was quenched with sodium sulfite (405.0 mg, 3.15 mmol) and acidified with 3 N HCl (1 mL). The reaction solution was partially concentrated in vacuo, and extracted with EtOAc (10 mL). The organic layer was concentrated in vacuo and purified by reverse phase HPLC (Waters Sunfire C18 19×100, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 80:20 A:B linear to 40:60 A:B in 8.5 min to 100% B to 9.0 min, hold at 100% B from 9.0 to 10.0 min. Flow: 25 mL/min) to give the title compound (6.8 mg, 6% yield). MS (ES+) 286.2 (M+1)+. Retention time=2.73 minutes (Waters Atlantis dC18 4.6×50, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Workup

  1. temperatureThe reaction mixture was heated to 50° C. for one hour
  2. temperaturecooled to room temperature
  3. stirringstirred for another 16 hours
  4. concentrationThe reaction solution was partially concentrated in vacuo
  5. extractionextracted with EtOAc (10 mL)
  6. concentrationThe organic layer was concentrated in vacuo
  7. custompurified by reverse phase HPLC (Waters Sunfire
  8. waitGradient: 80:20 A:B linear to 40:60 A:B in 8.5 min to 100% B to 9.0 min
  9. waithold at 100% B from 9.0 to 10.0 min

Sources & evidence

ORD record
ord-5a26f4525e49402b8198da9feac12bdc
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

Loading…