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 1393526노트

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HRID 1393526 반응식
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]

참가 물질

5

반응물 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

생성물 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-one수율 87%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-20 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0484f1df1789424393b3fbf07db0e449
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07345074B2

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