Pyridine → HCID 86697410, compound

HRID 2276717Notes

Reaction equation

HRID 2276717 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]23[CH:13]([CH:14]=O)[CH:12]2[CH2:11][N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9]3)=[CH:4][CH:3]=1.C1(=O)NC(=O)C=C1.ClC1C=CC(N)=CC=1.N1C=CC=CC=1.Cl.[CH3:45][O:46][NH2:47]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]23[CH:13]([CH:14]=[N:47][O:46][CH3:45])[CH:12]2[CH2:11][N:10]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:9]3)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 1049PyridineHCID 78124-ChloroanilineHCID 10935MaleimideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 86697411HCID 86697411, compound

Product 1

HCID 86697410HCID 86697410, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of tert-butyl 1-(4-chlorophenyl)-6-formyl-3-azabicyclo[3.1.0]hexane-3-carboxylate (609 mg, 1.99 mmol, prepared from maleimide and 4-chloroaniline according to the methods described in WO 2009141412 and WO 2008074716), in ethanol (10 mL) under nitrogen atmosphere, were added pyridine (0.8 mL, 9.9 mmol) and O-methylhydroxylamine hydrochloride (332.4 mg, 3.98 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, 2:3 EtOAc:Pet Ether) to afford pure tert-butyl 1-(4-chlorophenyl)-6-((methoxyimino)methyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate (430 mg, 63%) as a viscous oil as 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, 2:3 EtOAc:Pet Ether)

Sources & evidence

ORD record
ord-d06f034b94cc481cb4dfa0f06348b0ea
Source dataset
uspto-grants-2015_09
Patent number
US09133116B2

Reaction notes

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