Ammonium Chloride → 2-Amino-3-methoxybenzaldehyde

HRID 2055956Notes

Reaction equation

HRID 2055956 reaction equation
COC1C=CC=C2C=1N=C(N)N=C2.[CH3:14][O:15][C:16]1[C:17]([N+:24]([O-])=O)=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=[O:20].[NH4+].[Cl-]>CO.[Fe]>[NH2:24][C:17]1[C:16]([O:15][CH3:14])=[CH:23][CH:22]=[CH:21][C:18]=1[CH:19]=[O:20]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 988673-Methoxy-2-nitrobenzaldehydeHCID 167482158-Methoxyquinazolin-2-amine

Product 1

HCID 139701212-Amino-3-methoxybenzaldehydeYield 31.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

8-Methoxy-quinazolin-2-ylamine. To a solution of 3-methoxy-2-nitro-benzaldehyde (14.8 g, 81 mmol, Aldrich) and NH4Cl (4.4 g, 82 mmol, Aldrich) in 80% aq. MeOH (250 mL) was added iron dust (20.5 g, 367 mmol, Aldrich) and the reaction mixture was heated at 60° C. with stirring for 2 h. The reaction mixture was allowed to cool to room temperature and filtered through a pad of Celite®. The filter cake was washed with MeOH and the solution was concentrated in vacuum. The concentrated aq. solution was extracted with CH2Cl2 and the combined organic layers were washed with brine and dried over Na2SO4. Purification with EtOAc/Hexanes (0:1→1:4) as eluant gave 3.84 g (31%) of 2-amino-3-methoxy-benzaldehyde as a yellow oil. This oil was heated at 190C for 2.5 h in the presence of guanidine hydrochloride (4.9 g, 51 mmol, Aldrich), Na2CO3 (5.4 g, 51 mmol) and decalin (55 mL). The reaction was decanted while hot and the solution was allowed to cool to room temperature. The resultant precipitate was stirred with hexanes, filtered, washed with hexanes, and dried in vacuum to give the title compound as a yellow amorphous solid. MS (ESI, pos ion.) m/z: 176 (M+1).

Workup

  1. temperatureto cool to room temperature
  2. filtrationfiltered through a pad of Celite®
  3. washThe filter cake was washed with MeOH
  4. concentrationthe solution was concentrated in vacuum
  5. extractionThe concentrated aq. solution was extracted with CH2Cl2
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. customPurification with EtOAc/Hexanes (0:1→1:4) as eluant

Sources & evidence

ORD record
ord-eff1ec1bcdc94c71b6f969a5160e80f9
Source dataset
uspto-grants-2008_02
Patent number
US07332511B2

Reaction notes

Loading…