Dimethylformamide → 6-bromo-N-methyl-2-naphtamide

HRID 922708Notes

Reaction equation

HRID 922708 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([OH:14])=O)[CH:6]=[CH:5]2.[CH3:15][N:16](C)C=O.S(Cl)(Cl)=O.C(N(CC)CC)C.CO.CN>C(OCC)(=O)C.O.CN(C)C(=O)C.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([NH:16][CH3:15])=[O:14])[CH:6]=[CH:5]2

Participants

10

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 45498526-Bromo-2-naphthalenecarboxylic acidHCID 57454252Monomethylamine methanol

Product 1

HCID 218796286-bromo-N-methyl-2-naphtamideYield 89%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

6-Bromo-2-naphthoic acid (10.1 g, 40.1 mmol) and N,N-dimethylformamide (4.75 g, 65.0 mmol) were added to toluene (80 mL). To the reaction mixture was added dropwise thionyl chloride (5.7 g, 48.2 mmol) at 45 to 50° C., and the mixture was stirred for 1 hr, and allowed to cool to room temperature. The reaction mixture was added dropwise at 10 to 25° C. to a solution prepared by adding triethylamine (11.4 g, 112.4 mmol) and 40% methylamine methanol solution (8.1 g, 104.4 mmol) to toluene (80 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added dropwise water (50 mL), and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with a mixed solvent (25 mL) of methanol/water (2:8) to give wet crystals. The total amount of the wet crystals was added to N,N-dimethylacetamide (70 mL), and dissolved with heating to 60° C. The reaction mixture was allowed to cool to room temperature, and water (140 mL) was added dropwise thereto. The crystals were collected by filtration, and washed with water (80 mL) to give wet crystals. The total amount of the wet crystals was suspended in ethyl acetate (25 mL) with stirring at room temperature. The crystals were collected by filtration, and washed with ethyl acetate (5 mL). The obtained wet crystals were dried under reduced pressure to give 6-bromo-N-methyl-2-naphthamide (9.4 g, 35.6 mmol). yield 89%.

Workup

  1. additionThe reaction mixture was added dropwise at 10 to 25° C. to a solution
  2. customprepared
  3. stirringthe mixture was stirred at room temperature for 1 hr
  4. stirringthe mixture was stirred at room temperature
  5. filtrationThe crystals were collected by filtration
  6. washwashed with a mixed solvent (25 mL) of methanol/water (2:8)
  7. customto give wet crystals
  8. dissolutiondissolved
  9. temperaturewith heating to 60° C
  10. temperatureto cool to room temperature
  11. filtrationThe crystals were collected by filtration
  12. washwashed with water (80 mL)
  13. customto give wet crystals
  14. stirringwith stirring at room temperature
  15. filtrationThe crystals were collected by filtration
  16. washwashed with ethyl acetate (5 mL)
  17. customThe obtained wet crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-9bf6b4b530e34f16b80f13ea9660f441
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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