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2-Methoxyaniline → 4-Chloromethyl-N-(2-methoxyphenyl)-N-(1,3-dioxolan-2-yl)methylbenzamide

HRID 2456
Notes
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Reaction equation

HRID 2456 reaction equation
[CH3:1][O:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.Br[CH2:18][CH:19]1[O:23][CH2:22][CH2:21][O:20]1.[OH-].[Na+].[Cl:26][CH2:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1>C(Cl)Cl>[Cl:26][CH2:27][C:28]1[CH:36]=[CH:35][C:31]([C:32]([N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH2:18][CH:19]2[O:23][CH2:22][CH2:21][O:20]2)=[O:33])=[CH:30][CH:29]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 70002-MethoxyanilineHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 701364-(Chloromethyl)benzoyl chlorideHCID 780681,3-Dioxolane, 2-(bromomethyl)-

Product 1

HCID 196900064-Chloromethyl-N-(2-methoxyphenyl)-N-(1,3-dioxolan-2-yl)methylbenzamide
Yield 47.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

In an atmosphere of argon, a mixture consisting of o-anisidine (500 mg, 4.06 mmol), triethylamine (1.6 ml, 11.5 mmol) and 2-bromomethyl-1,3-dioxolan (0.96 ml, 8.18 mmol) was stirred at 80° C. for 4 days, dissolved in methylene chloride (8 ml) and then, with cooling in an ice bath, mixed with 20% sodium hydroxide aqueous solution (4 ml) and 4-chloromethylbenzoyl chloride (768 mg, 4.06 mmol). After 1 hour of stirring at the same temperature, the resulting mixture was extracted with methylene chloride, washed with 10% citric acid aqueous solution and saturated brine and then dried on anhydrous sodium sulfate. Thereafter, the solvent was removed by evaporation, and the resulting residue was purified by subjecting it to a silica gel column chromatography (ethyl acetate:hexane=2:5) to obtain 704 mg (47.9%) of the title compound in the form of colorless solid.

Workup

  1. temperaturewith cooling in an ice bath
  2. stirringAfter 1 hour of stirring at the same temperature
  3. extractionthe resulting mixture was extracted with methylene chloride
  4. washwashed with 10% citric acid aqueous solution and saturated brine
  5. dry with materialdried on anhydrous sodium sulfate
  6. customThereafter, the solvent was removed by evaporation
  7. customthe resulting residue was purified

Sources & evidence

ORD record
ord-15921a54043f4c95b9921819784b62d3
Source dataset
uspto-grants-1998_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05728835

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes