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

HRID 2044767Notes

Reaction equation

HRID 2044767 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.C([Li])CCC.[C:21]([N:40]1[CH:44]=[C:43]([CH:45]=[O:46])[N:42]=[CH:41]1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[Cl-].[NH4+]>CCCCCC.C1COCC1>[OH:46][CH:45]([C:43]1[N:42]=[CH:41][N:40]([C:21]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:44]=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 4

HCID 25517Ammonium ChlorideHCID 6182331-(triphenylmethyl)-1H-imidazole-4-carbaldehydeHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418339Butyllithium

Product 1

HCID 574658056-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamideYield 50.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
50 °C

Procedure

Under nitrogen atmosphere, 5.8 liters of THF was added to 105.6 g (0.40 mol, 1.2 eq) of 6-bromo-N-methyl-2-naphtamide, the mixture was warmed to 50° C. to dissolve it. 500 mL (0.50 mol, 2.4 eq) of a 1.6 M solution of n-butyllithium in hexane was added dropwise at −65° C. or lower over 35 minutes. The mixture was stirred at −65° C. for 1 hour. A solution of 112.7 g (0.33 mol) of 1-trityl-4-formyl-1H-imidazole in 810 mL of THF was added dropwise at −65° C. or lower over 40 minutes. The mixture was stirred at −65° C. for 2 hours. 1.5 Liters of an aqueous saturated ammonium chloride solution was added dropwise at −20° C. or lower, and the mixture was warmed to 30° C. After separation of the layers, the organic layer was washed with 1.5 liters of an aqueous saturated sodium chloride solution two times. After concentration under reduced pressure, 1 liter of ethyl acetate was added to the residue, and the mixture was stirred at 25° C. for 3 hours. Crystals were filtered, and washed with ethyl acetate. Vacuum drying (50° C.) to a constant weight afforded 87.9 g of 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (yield 50%).

Workup

  1. dissolutionto dissolve it
  2. stirringThe mixture was stirred at −65° C. for 2 hours
  3. temperaturelower, and the mixture was warmed to 30° C
  4. customAfter separation of the layers
  5. washthe organic layer was washed with 1.5 liters of an aqueous saturated sodium chloride solution two times
  6. concentrationAfter concentration under reduced pressure, 1 liter of ethyl acetate
  7. additionwas added to the residue
  8. stirringthe mixture was stirred at 25° C. for 3 hours
  9. filtrationCrystals were filtered
  10. washwashed with ethyl acetate
  11. customVacuum drying (50° C.) to a constant weight

Sources & evidence

ORD record
ord-d27a4fc483c642758f2724e9396e137d
Source dataset
uspto-grants-2013_11
Patent number
US08586762B2

Reaction notes

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