Ammonium Chloride → 6-(hydroxy(1-tosyl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

HRID 922723Notes

Reaction equation

HRID 922723 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([NH:14][CH3:15])=[O:13])[CH:6]=[CH:5]2.O1CCCC1.C([Mg]Cl)(C)C.CCCCCC.C([Li])CCC.[S:37]([N:47]1[CH:51]=[C:50]([CH:52]=[O:53])[N:49]=[CH:48]1)([C:40]1[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=1)(=[O:39])=[O:38].[Cl-].[NH4+]>O1CCCC1.CC(C)=O>[OH:53][CH:52]([C:50]1[N:49]=[CH:48][N:47]([S:37]([C:40]2[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=2)(=[O:39])=[O:38])[CH:51]=1)[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([C:12]([NH:14][CH3:15])=[O:13])[CH:6]=[CH:5]2

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 117157721-[(4-Methylphenyl)sulfonyl]-1H-imidazole-4-carboxaldehydeHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418244HCID 178418244, compoundHCID 178420664HCID 178420664, compound

Product 1

HCID 711172346-(hydroxy(1-tosyl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamideYield 52%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

Under a nitrogen atmosphere, 6-bromo-N-methyl-2-naphthamide (10.0 g, 37.9 mmol) was added to tetrahydrofuran (250 mL), and to the obtained solution was added dropwise 2.0 mol/L isopropylmagnesium chloride tetrahydrofuran solution (18.9 mL) at room temperature. The obtained reaction mixture was cooled to −30° C., 1.65 mol/L n-butyllithium hexane solution (37.9 mL) was added dropwise thereto, and the mixture was stirred at the same temperature for 1 hr or more. To the obtained reaction mixture was added dropwise a solution of 1-tosyl-4-formyl-1H-imidazole (14.2 g, 56.8 mmol) in tetrahydrofuran (200 mL) at −20° C., and the mixture was stirred at the same temperature for 2 hr. The obtained reaction mixture was warmed over 2 hr to 0° C., 20 w/v % aqueous ammonium chloride solution (150 mL) was added dropwise thereto. The separated organic layer was concentrated to the volume of about 130 mL under reduced pressure to give a residue. To the obtained residue was added tetrahydrofuran (200 mL), and the mixture was concentrated to the volume of about 130 mL under reduced pressure to give a residue. To the obtained residue was added acetone (200 mL), and the mixture was concentrated to the volume of about 200 mL under reduced pressure. These operations were repeated three times to give a residue. To the obtained residue was added acetone to adjust the volume to about 260 mL. The obtained solution was stirred at room temperature for 2 hr or more. The obtained crystals were collected by filtration, and washed with acetone (100 mL) to give wet crystals. The obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C. to give 6-(hydroxy(1-tosyl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide (8.5 g, 19.5 mmol). yield 52%.

Workup

  1. customThe obtained reaction mixture
  2. customTo the obtained reaction mixture
  3. stirringthe mixture was stirred at the same temperature for 2 hr
  4. customThe obtained reaction mixture
  5. additionwas added dropwise
  6. concentrationThe separated organic layer was concentrated to the volume of about 130 mL under reduced pressure
  7. customto give a residue
  8. concentrationthe mixture was concentrated to the volume of about 130 mL under reduced pressure
  9. customto give a residue
  10. concentrationthe mixture was concentrated to the volume of about 200 mL under reduced pressure
  11. customto give a residue
  12. stirringThe obtained solution was stirred at room temperature for 2 hr or more
  13. filtrationThe obtained crystals were collected by filtration
  14. washwashed with acetone (100 mL)
  15. customto give wet crystals
  16. customThe obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C.

Sources & evidence

ORD record
ord-97a980bfb29648b2ade9884261b29eea
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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