Benzene, 1-bromo-2-(trifluoromethyl)- → 6-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

HRID 922709Notes

Reaction equation

HRID 922709 reaction equation
BrC1C=CC=CC=1C(F)(F)F.CCCCCC.C([Li])CCC.Br[C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]2.[C:38]([N:57]1[CH:61]=[C:60]([CH:62]=[O:63])[N:59]=[CH:58]1)([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[Cl-].[NH4+]>C1COCC1>[OH:63][CH:62]([C:60]1[N:59]=[CH:58][N:57]([C:38]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:61]=1)[C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]2

Participants

7

Reactant 5

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 25517Ammonium ChlorideHCID 6182331-(triphenylmethyl)-1H-imidazole-4-carbaldehydeHCID 218796286-bromo-N-methyl-2-naphtamideHCID 178418244HCID 178418244, compound2×

Product 1

HCID 574658056-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamideYield 69.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

Under a nitrogen atmosphere, o-bromotrifluoromethylbenzene (1.35 kg, 6.00 mol) was added to tetrahydrofuran (7.9 L). The reaction mixture was cooled to −70° C., 1.6 mol/L n-butyllithium hexane solution (3.75 L, 6.00 mol) was added dropwise thereto, and the mixture was stirred at the same temperature for about 30 min. The reaction mixture was added dropwise at the same temperature to a solution prepared by adding 6-bromo-N-methyl-2-naphthamide (1.13 kg, 4.28 mol) to THF (62.2 L) at −70° C. under a nitrogen atmosphere, and the mixture was stirred for 1.5 hr. To the reaction mixture were added dropwise successively 1.6 mol/L n-butyllithium hexane solution (2.67 L, 4.27 mol) and a solution of 1-trityl-4-formyl-1H-imidazole (1.21 kg, 3.58 mol) in THF (7.9 L) at the same temperature, and the mixture was stirred for 2 hr. The reaction mixture was allowed to warm to −10° C., and 20 w/v % aqueous ammonium chloride solution (17.0 L) was added dropwise thereto at −10 to 0° C. The separated organic layer was concentrated under reduced pressure. To the residue was added ethyl acetate (11.3 L), and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with ethyl acetate (11.3 L). The obtained wet crystals were dried under reduced pressure to give 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (1.31 kg, 2.50 mol). yield 58%.

Workup

  1. additionThe reaction mixture was added dropwise at the same temperature to a solution
  2. customprepared
  3. stirringthe mixture was stirred for 1.5 hr
  4. temperatureto warm to −10° C.
  5. customat −10 to 0° C
  6. concentrationThe separated organic layer was concentrated under reduced pressure
  7. additionTo the residue was added ethyl acetate (11.3 L)
  8. stirringthe mixture was stirred at room temperature
  9. filtrationThe crystals were collected by filtration
  10. washwashed with ethyl acetate (11.3 L)
  11. customThe obtained wet crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-af5946ea5e03428ca3023e70188bf9f7
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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