1-Chloro-4-(chloromethyl)benzene → 3-[(4-Chlorophenyl)methyl]-2-pyrrolidinone

HRID 496211

反応式

HRID 496211 の反応式
C(NC(C)C)(C)C.C([Li])CCC.C[Si](C)(C)[N:15]1[CH2:19][CH2:18][CH2:17][C:16]1=[O:20].[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Cl)=[CH:26][CH:25]=1>C1COCC1.O>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][CH:17]2[CH2:18][CH2:19][NH:15][C:16]2=[O:20])=[CH:26][CH:25]=1

参加物

7

反応物 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 7912DiisopropylamineHCID 844611-(Trimethylsilyl)pyrrolidin-2-oneHCID 178418339Butyllithium

生成物 1

HCID 223136603-[(4-Chlorophenyl)methyl]-2-pyrrolidinone収率 20%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-76 °C

実験手順

In a flask was added diisopropylamine (3.22 g, 31.8 mmole) and dry THF (60 ml). The content of the flask was kept under nitrogen, and was then cooled to −76° C. To the cool solution was dropwise added n-butyllithium (n-BuLi, 32 mmole, 20 ml, 1.6 M in hexane). After completed addition, the solution was stirred for 10 minutes, and a solution of 1-Trimethylsilanyl-pyrrolidin-2-one (5.00 g, 31.8 mmole, prepared according to literature methods) in dry THF (5 ml) was added dropwise. The solution was then stirred for an additional 20 minutes and a solution of 4-Chlorobenzyl chloride (5.13 g, 32 mmole) in THF (5 ml) was added via a syringe during 5 minutes. The resulting mixture was stirred at −76° C. for 1 hour, and was then allowed to reach the ambient temperature and was stirred over night. Water (40 ml) was added and the mixture was stirred vigorously for 60 minutes. The phases were separated and the organic phase was washed with brine, and was finally evaporated, giving an oil which crystallized on standing. The solid was triturated with heptane:EtOAc 2:1 and was filtered, giving a partly purified solid. The solid was purified on silica (DCM to DCM: MeOH 99:1 to 98:2 to 97:3 gradient) giving 1.3 g (20%) of the sub-title compound.

後処理

  1. additionaddition
  2. stirringThe solution was then stirred for an additional 20 minutes
  3. stirringThe resulting mixture was stirred at −76° C. for 1 hour
  4. customthe ambient temperature
  5. stirringwas stirred over night
  6. stirringthe mixture was stirred vigorously for 60 minutes
  7. customThe phases were separated
  8. washthe organic phase was washed with brine
  9. customwas finally evaporated
  10. customgiving an oil which
  11. customcrystallized
  12. customThe solid was triturated with heptane:EtOAc 2:1
  13. filtrationwas filtered
  14. customgiving a partly purified solid
  15. customThe solid was purified on silica (DCM to DCM: MeOH 99:1 to 98:2 to 97:3 gradient)

出典と根拠

ORDレコード
ord-70c9776517aa4c38af74b4a56fa4fe34
出典データセット
uspto-grants-2005_09
特許番号
US06943188B2

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