Water → N-(5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamide

HRID 1357305Notes

Reaction equation

HRID 1357305 reaction equation
B(Cl)(Cl)Cl.[Br:5][C:6]1[C:15]([O:16]C)=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([CH2:18][N:19]([CH3:34])[C:20](=[O:33])[C:21]1[CH:26]=[CH:25][C:24]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[CH:23][CH:22]=1)=[CH:11]2.C(=O)=O.CC(C)=O.O>C(Cl)Cl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:5][C:6]1[C:15]([OH:16])=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][C:10]([CH2:18][N:19]([CH3:34])[C:20](=[O:33])[C:21]1[CH:22]=[CH:23][C:24]([CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)=[CH:25][CH:26]=1)=[CH:11]2

Participants

7

Reactant 4

HCID 962WaterHCID 25135Boron TrichlorideHCID 18505333N-(5-bromo-6-methoxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamideHCID 18522661Acetone cardice

Product 1

HCID 18505343N-(5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamideYield 98.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Boron trichloride (5.5 mL of a 1 M solution in methylene chloride; 5.5 mmol) was added under argon to a solution of N-(5-bromo-6-methoxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamide (860 mg, 1.8 mmol), prepared by the general acylation procedure described above, and tetrabutylammonium iodide (2.04 g, 5.5 mmol) in 10 mL of methylene chloride at dry ice-acetone temperature. After the addition the reaction was allowed to warm to room temperature. The reaction was considered finished after HPLC/TLC analysis indicated the formation of a single product and the disappearance of the starting amide. The reaction was cooled to ice bath temperature followed by the addition of water. The organic layer was separated and the aqueous layer extracted three times with methylene chloride. The combined extracts were dried (Na2SO4) and the solvent removed under reduced pressure. The residue was purified by column chromatography (20-30% ethyl acetate in hexanes) to give N-(5-bromo-6-hydroxy-naphthalen-2-ylmethyl)-4-cyclohexyl-N-methyl-benzamide (799 mg, 97%), LCMS (Calc'd: 451.13; Found: 451.65).

Workup

  1. customprepared by the general acylation procedure
  2. additionAfter the addition the reaction
  3. temperatureThe reaction was cooled to ice bath temperature
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted three times with methylene chloride
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by column chromatography (20-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5f8b7acf9862483ab44a2a7d61068219
Source dataset
uspto-grants-2003_07
Patent number
US06589970B2

Reaction notes

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