1-(Bromomethyl)-4-(trifluoromethoxy)benzene → (2R,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-one

HRID 23837

Reaction equation

HRID 23837 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([C@@H:15]1[N:19]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C:18](=[O:28])[C@@H:17]([CH3:29])[N:16]1[C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])([CH3:14])([CH3:13])[CH3:12].[F:36][C:37]([F:48])([F:47])[O:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Br)=[CH:41][CH:40]=1>C1COCC1>[C:11]([C@@H:15]1[N:19]([C:20]2[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=2)[C:18](=[O:28])[C@@:17]([CH3:29])([CH2:43][C:42]2[CH:45]=[CH:46][C:39]([O:38][C:37]([F:48])([F:47])[F:36])=[CH:40][CH:41]=2)[N:16]1[C:30](=[O:35])[C:31]([F:33])([F:34])[F:32])([CH3:12])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzeneHCID 2733832Lithium HexamethyldisilazideHCID 11188674(2S,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-imidazolidin-4-one

Product 1

HCID 59979238(2R,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-oneYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

Lithium bis(trimethylsilyl)amide (LiHMDS) (38.0 mL, 1 M in THF) was added slowly dropwise over 25 min to a solution of (2S,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-imidazolidin-4-one (10.0 g, 25.17 mmol) in 60 mL of THF at −20° C. After stirring at −20° C. for 20 min, a solution of 4-trifluoromethoxybenzyl bromide (6.04 mL, 37.76 mmol) in 30 mL of THF was added dropwise over 20 min. The mixture was stirred at −20° C. for 45 min, warmed to −5° C. over 1 h, and then poured over 50 mL of ice-cold saturated NH4Cl solution. The resulting mixture was extracted with two portions of EtOAc (200,100 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was triturated with hexanes to afford 12.5 g (87%) of (2R,5R)-2-tert-butyl-3-(3,5-dichloro-phenyl)-5-methyl-1-(2,2,2-trifluoro-acetyl)-5-(4-trifluoromethoxy-benzyl)-imidazolidin-4-one as an off-white solid.

Workup

  1. stirringThe mixture was stirred at −20° C. for 45 min
  2. temperaturewarmed to −5° C. over 1 h
  3. extractionThe resulting mixture was extracted with two portions of EtOAc (200,100 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was triturated with hexanes

Sources & evidence

ORD record
ord-053189239f1f4521a22f5784723eb894
Source dataset
uspto-grants-2005_02
Patent number
US06852748B1

Linked notes

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