Hydrochloric Acid → HCID 22139706, compound

HRID 1825867Notes

Reaction equation

HRID 1825867 reaction equation
Cl.[F:2][C:3]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:4]=1[O:5][C:6]1[C:15]([O:16][CH3:17])=[CH:14][C:13](N)=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2.N([O-])=O.[Na+].[OH-].[Na+]>O>[F:2][C:3]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:4]=1[O:5][C:6]1[C:15]([O:16][CH3:17])=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 22139705HCID 22139705, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 22139706HCID 22139706, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2.4 mL HCl in 24 mL H2O was heated to the boiling point and poured into 2.4 g (0.008 mol) of 5-(2,4-difluoro-phenoxy)-6-methoxy-quinolin-8-ylamine, then stirred while hot to dissolve as much solid as possible. The solution was cooled in an ice-salt mixture. When the temperature reached 15° C., 2.5 mL of conc. HCl were added to the reaction mixture. At 10° C. a solution of NaNO2 (1.1 g, 0.016 mol in 2 mL of water) was added dropwise during 10 min. The reaction mixture was stirred at 5–10° C. for 30 min., treated with ice-cold 30% H3PO4, and cooled at 0° C. overnight. After stirring for an additional 8 hours,at room temperature, the reaction mixture was neutralized with 1N NaOH, extracted with CH2Cl2, and the organic layer was dried (MgSO4). Solvent removal, followed by HPLC, eluting with 10–20% EtOAc/Hexane gave 1.5 g (66%) of 5-(2,4-difluoro-phenoxy)-6-methoxy-quinoline, which crystallized at room temperature.

Workup

  1. dissolutionto dissolve as much solid as possible
  2. customreached 15° C.
  3. stirringThe reaction mixture was stirred at 5–10° C. for 30 min.
  4. stirringAfter stirring for an additional 8 hours,at room temperature
  5. extractionextracted with CH2Cl2
  6. dry with materialthe organic layer was dried (MgSO4)
  7. customSolvent removal
  8. washeluting with 10–20% EtOAc/Hexane

Sources & evidence

ORD record
ord-557b9b7a702a4d838a3e5607078b6817
Source dataset
uspto-grants-2006_05
Patent number
US07049325B2

Reaction notes

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