4-Chloroaniline → 1-(4-Chlorophenyl)-2,5-bis(4-nitrophenyl)pyrrolidine

HRID 1470970

Reaction equation

HRID 1470970 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10](O)[CH2:11][CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)O)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[Cl:37][C:38]1[CH:44]=[CH:43][C:41]([NH2:42])=[CH:40][CH:39]=1>C(Cl)Cl.CN(C=O)C>[Cl:37][C:38]1[CH:44]=[CH:43][C:41]([N:42]2[CH:10]([C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11][CH2:12][CH:13]2[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 78124-ChloroanilineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59616924(1R,4R)-1,4-bis(4-nitrophenyl)butane-1,4-diol

Product 1

HCID 866491061-(4-Chlorophenyl)-2,5-bis(4-nitrophenyl)pyrrolidineYield 35.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

The product of Example 1B (0.50 g, 1.51 mmol) was suspended in CH2Cl2 (15 mL). Triethylamine (0.626 mL, 4.51 mmol) was added at 0° C., the resulting mixture was stirred for 30 min, and methanesulfonyl chloride (0.293 mL, 3.76 mmol) was added. The mixture was stirred at rt for 1 hr and then concentrated in vacuo to give a light yellow solid. The solid was dissolved in DMF (6 mL), 4-chloroaniline (1.92 g, 15.05 mmol) was added, and the resulting mixture was stirred at 50° C. overnight. The mixture was partitioned between EtOAc and 1N aq HCl, and the organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-12% EtOAc in hexane to give the title compound (0.226 g, 35%).

Workup

  1. stirringThe mixture was stirred at rt for 1 hr
  2. concentrationconcentrated in vacuo
  3. customto give a light yellow solid
  4. stirringthe resulting mixture was stirred at 50° C. overnight
  5. customThe mixture was partitioned between EtOAc and 1N aq HCl
  6. dry with materialthe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-12% EtOAc in hexane

Sources & evidence

ORD record
ord-98a74bb76e304355a55037d989a89499
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Linked notes

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