Ammonium Chloride → tert-Butyl N-[(3S)-1-(4-bromo-3-methylphenyl)-5-oxopyrrolidin-3-yl]carbamate

HRID 715924Notes

Reaction equation

HRID 715924 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[CH3:9].[O:10]=[C:11]1[NH:15][CH2:14][C@@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:12]1.[F-].[Cs+].CN(C)CCN.[Cl-].[NH4+]>C(#N)C.[Cu](I)I>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:15]2[C:11](=[O:10])[CH2:12][C@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH2:14]2)=[CH:4][C:3]=1[CH3:9]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 25953Cesium fluorideHCID 66053N,N-DimethylethylenediamineHCID 27355742-Bromo-5-iodotolueneHCID 45091936(S)-tert-Butyl (5-oxopyrrolidin-3-yl)carbamate

Product 1

HCID 117893476tert-Butyl N-[(3S)-1-(4-bromo-3-methylphenyl)-5-oxopyrrolidin-3-yl]carbamateYield 96.5%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2-bromo-5-iodotoluene (1.5 g), tert-butyl ((S)-5-oxopyrrolidin-3-yl)carbamate (2.7 g), copper iodide (95 mg), cesium fluoride (1.9 g), and N,N-dimethylethylenediamine (0.11 ml) in acetonitrile (20 ml) was stirred at 100° C. for 3 hours under a nitrogen atmosphere. After cooling, a saturated aqueous solution of ammonium chloride was added to the reaction solution, followed by extraction with ethyl acetate. The extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain the title compound (1.8 g).

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed with a 10% aqueous sodium thiosulfate solution and saturated saline in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-33b112249b754d16a700070604b8e3d4
Source dataset
uspto-grants-2015_11
Patent number
US09187489B2

Reaction notes

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