Aluminum(III) Chloride → 4-(6-Hydroxyquinazolin-2-yl)benzoic acid

HRID 1472674Notes

Reaction equation

HRID 1472674 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=1)[N:7]=[CH:6]2.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([C:13]1[CH:14]=[CH:15][C:16]([C:17]([OH:19])=[O:18])=[CH:20][CH:21]=1)[N:7]=[CH:6]2

Participants

4

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 679742014-(6-Methoxyquinazolin-2-yl)benzoic acid

Product 1

HCID 574071574-(6-Hydroxyquinazolin-2-yl)benzoic acidYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(6-methoxyquinazolin-2-yl)benzoic acid (220 mg, 0.785 mmol) in anhydrous CH2Cl2 (5 mL) was added AlCl3 (600 mg, 4.55 mmol), the reaction mixture was refluxed overnight. The mixture was quenched with sat.NH4Cl (10 mL), the aqueous layer was extracted with CH2Cl2/MeOH (v/v=10/1, 30 mL×3), the combined organic layer was washed with brine (30 mL), dried over Na2SO4, filtered and concentrated to give the crude product, which purified by prep-HPLC (0.1% TFA as additive) to give Compound V-1 (27 mg, yield 13%). 1H NMR (MeOD 400 MHz): δ 9.42 (s, 1H), 8.60 (d, J=8.4 Hz, 2H), 8.17 (d, J=8.4 Hz, 2H), 8.00 (d, J=9.2 Hz, 1H), 7.60 (dd, J=9.2, 2.8 Hz, 1H), 7.30 (d, J=2.8 Hz, 1H). MS (ESI): m/z 266.9 [M+H]+.

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customThe mixture was quenched
  3. extractionNH4Cl (10 mL), the aqueous layer was extracted with CH2Cl2/MeOH (v/v=10/1, 30 mL×3)
  4. washthe combined organic layer was washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-68e68d21a2424d8fbcc5c8b0cfd1579c
Source dataset
uspto-grants-2015_04
Patent number
US09012646B2

Reaction notes

Loading…