Methylamine → 2-(4-bromo-2-fluorophenyl)-N-methylacetamide

HRID 1525883Notes

Reaction equation

HRID 1525883 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](O)=[O:10])=[C:4]([F:12])[CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:19][NH2:20]>ClCCl.CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:20][CH3:19])=[O:10])=[C:4]([F:12])[CH:3]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acid

Product 1

HCID 712707042-(4-bromo-2-fluorophenyl)-N-methylacetamideYield 23.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(4-bromo-2-fluorophenyl)acetic acid (10.56 mmol) in dichloromethane (20 mL) was treated with oxalyl chloride (31.7 mmol) and dimethylformamide (0.106 mmol). Effervescense was observed for fifteen minutes. When the bubbling had ceased, the reaction was concentrated to dryness in vacuo. The resulting oil was dissolved with dichloromethane and was concentrated to dryness in vacuo. The material was then diluted with tetrahydrofuran (20 mL) and was treated with methanamine (31.7 mmol) dropwise. Effervescense was again observed. A precipitate formed as the reaction was stirred over a two hour period. The contents of the reaction were concentrated to dryness in vacuo and were then dissolved in a minimal amount of methanol. Ethyl acetate was then added to this solution until a solid precipitated. The precipitate was collected by vacuum filtration. In a similar manner, two additional crops were collected from the mother liquor. The resulting solids were combined and triturated with dichloromethane. Purification of the solid by silica gel chromatography (0-5% methanol/dichloromethane) afforded the title compound as a white solid (610 mg, 22% yield). MS(ES)+ m/e 246.0/247.8 [M+H]+ (bromide isotope pattern).

Workup

  1. waitEffervescense was observed for fifteen minutes
  2. concentrationthe reaction was concentrated to dryness in vacuo
  3. dissolutionThe resulting oil was dissolved with dichloromethane
  4. concentrationwas concentrated to dryness in vacuo
  5. additionThe material was then diluted with tetrahydrofuran (20 mL)
  6. customA precipitate formed as the reaction
  7. concentrationThe contents of the reaction were concentrated to dryness in vacuo
  8. dissolutionwere then dissolved in a minimal amount of methanol
  9. additionEthyl acetate was then added to this solution until a solid
  10. customprecipitated
  11. filtrationThe precipitate was collected by vacuum filtration
  12. customIn a similar manner, two additional crops were collected from the mother liquor
  13. customtriturated with dichloromethane
  14. customPurification of the solid by silica gel chromatography (0-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8c5d4916becf4adb846205686fe01976
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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