Ethyl Acetate → HCID 68289084, compound

HRID 541215Notes

Reaction equation

HRID 541215 reaction equation
I[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[O:10]=[C:11]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12]1.C(OCC)(=O)C>C1COCC1>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([C:11]2([OH:10])[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:13][CH2:12]2)=[CH:3][CH:4]=1)#[N:7]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 764674-IodobenzonitrileHCID 1512679N-Boc-hexahydro-1H-azepin-4-one

Product 1

HCID 68289084HCID 68289084, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of 4-iodobenzonitrile (510 mg, 2.22 mmol, 1.1 equiv) in THF (3 mL) was added to a 10 mL round-bottom flask and the system purged with nitrogen. The mixture was cooled to −40° C. then isopropylmagnesium chloride (1.16 mL of a 2.0 M soln in THF, 2.32 mmol, 1.15 equiv) was added dropwise over 20 minutes. The resulting mixture was stirred at −40° C. for 2 hours then tert-butyl 4-oxoazepane-1-carboxylate (431 mg, 2.02 mmol, 1.0 equiv) in THF (0.5 mL) was added dropwise over 15 minutes. The resulting mixture was stirred at −40° C. for 1 hour then diluted into ethyl acetate (15 mL) and washed with 0.2 M HCl (10 mL), 0.1 M HCl (5 mL), saturated sodium bicarbonate (5 mL) then brine (5 mL). The organics were dried (Na2SO4), filtered and evaporated. To remove remaining ketone and aldol by-product, the residue was dissolved in acetonitrile (3 mL) then hydrazine (0.2 mL) was added and heated at 60° C. for 4 hours. The mixture was diluted with EtOAc (20 mL) and washed with water (20 mL), followed by 0.5 M phosphoric acid (3×20 mL), saturated sodium bicarbonate (10 mL) and brine (10 mL). The organics were dried (Na2SO4), filtered and evaporated. The residue was purified by silica column chromatography (hexanes/ethyl acetate) to obtain the title compound as a pink oil which solidified upon standing (303 mg, 47%). m/z (ES+) 317 (M+H)+.

Workup

  1. customthe system purged with nitrogen
  2. additionisopropylmagnesium chloride (1.16 mL of a 2.0 M soln in THF, 2.32 mmol, 1.15 equiv) was added dropwise over 20 minutes
  3. stirringThe resulting mixture was stirred at −40° C. for 1 hour
  4. washwashed with 0.2 M HCl (10 mL), 0.1 M HCl (5 mL), saturated sodium bicarbonate (5 mL)
  5. dry with materialThe organics were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customTo remove
  9. dissolutionthe residue was dissolved in acetonitrile (3 mL)
  10. additionhydrazine (0.2 mL) was added
  11. temperatureheated at 60° C. for 4 hours
  12. additionThe mixture was diluted with EtOAc (20 mL)
  13. washwashed with water (20 mL)
  14. dry with materialThe organics were dried (Na2SO4)
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue was purified by silica column chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-1fb646424a074172bd5973c872d36229
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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