Pyridine → HCID 86697414, compound

HRID 2276722Notes

Reaction equation

HRID 2276722 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH:14]([CH:15]=O)[CH:13]2[CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8].C1(=O)NC(=O)C=C1.ClC1C=C(C=CC=1Cl)N.N1C=CC=CC=1.Cl.[CH3:47][O:48][NH2:49]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH:14]([CH:15]=[N:49][O:48][CH3:47])[CH:13]2[CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])=[O:18])[CH2:10]3)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 5

HCID 1049PyridineHCID 72573,4-DichloroanilineHCID 10935MaleimideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 75113129HCID 75113129, compound

Product 1

HCID 86697414HCID 86697414, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of tert-butyl 1-(3,4-dichlorophenyl)-6-formyl-3-azabicyclo[3.1.0]hexane-3-carboxylate (2.50 g, 7.02 mmol, prepared from maleimide and 3,4-dichloroaniline according to the methods described in WO 2009141412 and WO 2008074716), in ethanol (40 mL) under nitrogen atmosphere, were added pyridine (2.82 mL, 35.04 mmol) and O-methylhydroxylamine hydrochloride (1.17 g, 14.01 mmol). The reaction mixture was refluxed for 5 h. After completion of the reaction as confirmed by TLC, the solvent was evaporated. The crude compound was extracted with ethyl acetate (20 mL). The organic layer was separated, washed with 5% HCl (5 mL), water (10 mL), dried over Na2SO4 and concentrated in vacuo to afford crude product which was purified by column chromatography (silica gel, 1:9 EtOAc:Pet Ether) to afford pure tert-butyl 1-(3,4-dichlorophenyl)-6-((methoxyimino)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (2.45 g, 90%) as a viscous oil as a mixture of isomers.

Workup

  1. temperatureThe reaction mixture was refluxed for 5 h
  2. customAfter completion of the reaction
  3. customthe solvent was evaporated
  4. extractionThe crude compound was extracted with ethyl acetate (20 mL)
  5. customThe organic layer was separated
  6. washwashed with 5% HCl (5 mL), water (10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto afford crude product which
  10. customwas purified by column chromatography (silica gel, 1:9 EtOAc:Pet Ether)

Sources & evidence

ORD record
ord-893397a051ac4c6e995bab079328828d
Source dataset
uspto-grants-2015_09
Patent number
US09133116B2

Reaction notes

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