Imidazole → HCID 11427123, compound

HRID 2358234Notes

Reaction equation

HRID 2358234 reaction equation
[N:1]([C:4]1[C:5]([F:19])=[C:6]([CH:11]2[CH2:15][N:14]([CH2:16]O)[C:13](=[O:18])[CH2:12]2)[CH:7]=[CH:8][C:9]=1[F:10])=[N+:2]=[N-:3].[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1>C(Cl)Cl>[N:1]([C:4]1[C:5]([F:19])=[C:6]([CH:11]2[CH2:15][N:14]([CH2:16][N:20]3[CH:24]=[CH:23][N:22]=[CH:21]3)[C:13](=[O:18])[CH2:12]2)[CH:7]=[CH:8][C:9]=1[F:10])=[N+:2]=[N-:3]

Participants

4

Reactant 2

HCID 795ImidazoleHCID 58911269HCID 58911269, compound

Product 1

HCID 11427123HCID 11427123, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
28 °C

Procedure

In a 100 ml three necked flask fitted with a magnetic stirrer, under inert atmosphere, distilled tetramethyl-chloro-enamine (1.1 ml, 8.5 mmol) is added to a solution of 4-(3-azido-2,4-difluoro-phenyl)-1-hydroxymethyl-pyrrolidin-2-one a15 (1.9 g, 7.08 mmol) in CH2Cl2 (45 ml) at 0° C. After 3.5 h, the mixture is transferred via a canula into a second three necked flask fitted with a magnetic stirrer, under inert atmosphere, containing a solution of imidazole (2.4 g, 35.4 mmol) in CH2Cl2 (45 ml) at room temperature. The temperature raised up to 28° C. and a precipitate appears. After 1 h, the reaction mixture is filtered, evaporated in vacuo, diluted with CH2Cl2 and the organic layer is washed with water, dried over MgSO4, filtered and evaporated in vacuo. The residue is purified by chromatography on silicagel (CH2Cl2/EtOH/NH4OH: 93.5/06/0.5 (v/v)) to afford 4-(3-azido-2,4-difluoro-phenyl)-1-imidazol-1-ylmethyl-pyrrolidin-2-one 5 (1.66 g, 75%). The racemate is resolved by preparative chiral chromatography (Chiralpak AD, benzine/EtOH) and the enantiomers are recrystallized successively in toluene and AcOEt to afford the two enantiomers 6 (first eluted) and 7 (second eluted) as white solids (0.5 g and 0.45 g).

Workup

  1. customfitted with a magnetic stirrer, under inert atmosphere
  2. waitAfter 1 h
  3. filtrationthe reaction mixture is filtered
  4. customevaporated in vacuo
  5. additiondiluted with CH2Cl2
  6. washthe organic layer is washed with water
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue is purified by chromatography on silicagel (CH2Cl2/EtOH/NH4OH: 93.5/06/0.5 (v/v))

Sources & evidence

ORD record
ord-bfce86cb2d87461d982004282c24441f
Source dataset
uspto-grants-2010_07
Patent number
US07763644B2

Reaction notes

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