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

HRID 922713Notes

Reaction equation

HRID 922713 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.[C:37]([N:56]1[CH:60]=[C:59]([CH:61]=[O:62])[N:58]=[CH:57]1)([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[Cl-].[NH4+]>O1CCCC1>[OH:62][CH:61]([C:59]1[N:58]=[CH:57][N:56]([C:37]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:60]=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

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 6182331-(triphenylmethyl)-1H-imidazole-4-carbaldehydeHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418244HCID 178418244, compoundHCID 178420664HCID 178420664, compound

Product 1

HCID 574658056-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamideYield 74.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

Under a nitrogen atmosphere, 6-bromo-N-methyl-2-naphthamide (7.0 g, 26.5 mmol) was added to tetrahydrofuran (175 mL), and then 2.0 mol/L isopropylmagnesium chloride tetrahydrofuran solution (13.7 mL) was added dropwise thereto at room temperature. The reaction mixture was cooled to −30° C., 1.6 mol/L n-butyllithium hexane solution (26.6 mL) was added dropwise thereto, and the mixture was stirred at the same temperature for 2 hr. To the reaction mixture was added dropwise a solution of 1-trityl-4-formyl-1H-imidazole (13.5 g, 39.9 mmol) in tetrahydrofuran (140 mL) at −20° C., and the mixture was stirred at the same temperature for 2 hr. The reaction mixture was allowed to warm to 0° C., and stirred for 1 hr, and 20 w/v % aqueous ammonium chloride solution (105 mL) was added dropwise thereto. The organic layer was separated, and concentrated to the volume of about 90 mL under reduced pressure. To the residue was added tetrahydrofuran (140 mL), and the mixture was concentrated to the volume of about 90 mL under reduced pressure. To the residue was added acetone (140 mL), and the mixture was concentrated to the volume of about 140 mL under reduced pressure. These operations were repeated three times. To the residue was added acetone to adjust the volume to about 180 mL, and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with acetone (70 mL). The obtained wet crystals were dried under reduced pressure to give 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (10.3 g, 19.7 mmol). yield 74%.

Workup

  1. customat room temperature
  2. stirringthe mixture was stirred at the same temperature for 2 hr
  3. temperatureto warm to 0° C.
  4. stirringstirred for 1 hr
  5. customThe organic layer was separated
  6. concentrationconcentrated to the volume of about 90 mL under reduced pressure
  7. additionTo the residue was added tetrahydrofuran (140 mL)
  8. concentrationthe mixture was concentrated to the volume of about 90 mL under reduced pressure
  9. additionTo the residue was added acetone (140 mL)
  10. concentrationthe mixture was concentrated to the volume of about 140 mL under reduced pressure
  11. additionTo the residue was added acetone
  12. stirringthe mixture was stirred at room temperature
  13. filtrationThe crystals were collected by filtration
  14. washwashed with acetone (70 mL)
  15. customThe obtained wet crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-0fb557065a504146b8a4ea652faad662
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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