Phosgene → HCID 11277839, compound

HRID 2358242Notes

Reaction equation

HRID 2358242 reaction equation
C(Cl)(Cl)=O.[N+]([C:8]1[NH:9][CH:10]=[CH:11][N:12]=1)([O-])=O.C(N(CC)CC)C.O[CH2:21][N:22]1[CH2:26][CH:25]([C:27]2[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=2)[CH2:24][C:23]1=[O:36].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1>[F:33][C:31]1[CH:32]=[C:27]([CH:25]2[CH2:26][N:22]([CH2:21][N:9]3[CH:10]=[CH:11][N:12]=[CH:8]3)[C:23](=[O:36])[CH2:24]2)[CH:28]=[C:29]([F:35])[C:30]=1[F:34]

Participants

7

Reactant 5

HCID 6371PhosgeneHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 107012-NitroimidazoleHCID 11390912HCID 11390912, compound

Product 1

HCID 11277839HCID 11277839, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a 100 ml three necked flask fitted with a magnetic stirrer, under inert atmosphere, phosgene (20 wt % in toluene, 0.95 eq, 2.02 mmol, 1 g) was added dropwise at room temperature to a solution of 2-nitroimidazole (2.5 eq, 5.1 mmol, 0.577 g) and triethylamine (3 eq, 6.1 mmol, 0.628 g, 0.85 ml) in THF (30 ml). After 0.5 h, 1-hydroxymethyl-4-(3,4,5-trifluoro-phenyl)-pyrrolidin-2-one a23 (1 eq, 2.1 mmol, 0.5 g) in THF (5 ml) was added dropwise at room temperature. After 4 h, the crude mixture was pored into a mixture of ice-cooled saturated sodium carbonate. After extraction (AcOEt), drying of the cumulated organic layers (MgSO4), filtration and evaporation of the solvents, the crude mixture was purified by flash chromatography on silicagel (dichloromethane/methanol: 98/2 (v/v)) to give, after recrystallization in AcOEt, 1-(2-nitro-imidazol-1-ylmethyl)-4-(3,4,5-trifluoro-phenyl)-pyrrolidin-2-one 40 (138 mg, 20.3%).

Workup

  1. waitAfter 4 h
  2. extractionAfter extraction (AcOEt)
  3. dry with materialdrying of the cumulated organic layers (MgSO4), filtration and evaporation of the solvents
  4. customthe crude mixture was purified by flash chromatography on silicagel (dichloromethane/methanol: 98/2 (v/v))
  5. customto give
  6. customafter recrystallization in AcOEt

Sources & evidence

ORD record
ord-3842e3a421314dd39a7ae572d0d87336
Source dataset
uspto-grants-2010_07
Patent number
US07763644B2

Reaction notes

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