Pyridine → HCID 86697412, compound

HRID 2276719Notes

Reaction equation

HRID 2276719 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.Cl.[NH2:41][OH:42].N1C=CC=CC=1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH:14]([CH:15]=[N:41][OH:42])[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]

Participants

7

Reactant 5

HCID 1049PyridineHCID 72573,4-DichloroanilineHCID 10935MaleimideHCID 443297Hydroxyamine hydrochlorideHCID 75113129HCID 75113129, compound

Product 1

HCID 86697412HCID 86697412, compoundYield 73%

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 (200 mg, 0.56 mmol, prepared from maleimide and 3,4-dichloroaniline according to the methods described in WO 2009141412 and WO 2008074716), in ethanol (10 mL) under nitrogen atmosphere were added hydroxylamine hydrochloride (78 mg, 1.12 mmol) and pyridine (0.23 mL, 2.86 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 (70 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, 1:4 EtOAc:Pet Ether) to afford pure tert-butyl 1-(3,4-dichlorophenyl)-6-((hydroxyimino)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (152 mg, 73%) 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 (70 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, 1:4 EtOAc:Pet Ether)

Sources & evidence

ORD record
ord-71cdf40930b44b7e82113a1528a586ae
Source dataset
uspto-grants-2015_09
Patent number
US09133116B2

Reaction notes

Loading…