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 733328Notes

Reaction equation

HRID 733328 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 EtOAc. 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 EtOAc
  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-6436de216daf46d3bcec38e47c227fe0
Source dataset
uspto-grants-2009_09
Patent number
US07589115B2

Reaction notes

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