Ammonium Chloride → 2-Amino-3-methoxybenzaldehyde

HRID 857639Notes

Reaction equation

HRID 857639 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 2amino-3-methoxy-benzaldehyde as a yellow oil. This oil was heated at 190° C. 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-0e12df9760054ffdb03072f257616a8a
Source dataset
uspto-grants-2006_12
Patent number
US07144888B2

Reaction notes

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