Ammonium formate → 4-(4-Amino-2-fluorophenoxy)quinolin-7-ol

HRID 2277373Notes

Reaction equation

HRID 2277373 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][C:21]=3[F:29])=[CH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>[Pd].CCO.O>[NH2:26][C:23]1[CH:24]=[CH:25][C:20]([O:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([OH:8])=[CH:10][CH:11]=3)[N:16]=[CH:15][CH:14]=2)=[C:21]([F:29])[CH:22]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 681938637-(Benzyloxy)-4-(2-fluoro-4-nitrophenoxy)quinoline

Product 1

HCID 1363502984-(4-Amino-2-fluorophenoxy)quinolin-7-olYield 96.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
30 °C

Procedure

To a mixture of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)quinoline (16.38 g, 42 mmol) and HCOONH4 (26.46 g, 420 mmol) in a mixture solution of EtOH/H2O (84 mL, v/v=4:1) was added a catalytic amount of Pd/C (0.50 g, 5% amount, 53%˜55% water content, w/w). The reaction was stirred at 30° C. for 24 hours, and was monitored by LC-MS. After the complete consumption of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)quinoline, 6 M HCl (80 mL) was added to the reaction mixture until the solid was dissolved. The resulted solution was filtered. Saturated aqueous NaHCO3 solution (210 mL) was added to the filtrate to adjust the final pH to 6.0˜6.5 followed by the addition of a mixture of water (20 mL) and CH2Cl2 (50 mL). The resulted mixture was stirred at room temperature for 4 hours. The solid was collected by filtration, washed with a mixture of MeOH/DCM (50 mL, v/v=1/1), and dried in vacuo at 45° C. to give the title compound as a light yellow solid (11.0 g, 92%).

Workup

  1. customAfter the complete consumption of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)quinoline, 6 M HCl (80 mL)
  2. additionwas added to the reaction mixture until the solid
  3. dissolutionwas dissolved
  4. filtrationThe resulted solution was filtered
  5. additionSaturated aqueous NaHCO3 solution (210 mL) was added to the filtrate
  6. additionfollowed by the addition of a mixture of water (20 mL) and CH2Cl2 (50 mL)
  7. stirringThe resulted mixture was stirred at room temperature for 4 hours
  8. filtrationThe solid was collected by filtration
  9. washwashed with a mixture of MeOH/DCM (50 mL, v/v=1/1)
  10. customdried in vacuo at 45° C.

Sources & evidence

ORD record
ord-c21d2fa917af4dac86c0ae6c8a9a19a6
Source dataset
uspto-grants-2015_09
Patent number
US09133162B2

Reaction notes

Loading…