Hydrogen chloride-ethyl acetate → 8-Isopropoxy-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine

HRID 2191255Notes

Reaction equation

HRID 2191255 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][N:10](C(OC(C)(C)C)=O)[CH2:11][CH2:12][O:13][C:14]=2[N:15]=1)([CH3:3])[CH3:2].Cl.C(OCC)(=O)C>C(OCC)(=O)C>[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][NH:10][CH2:11][CH2:12][O:13][C:14]=2[N:15]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 68429626tert-Butyl 8-isopropoxy-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 426015108-Isopropoxy-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepineYield 7.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the compound obtained in Example 4, step 1 (0.60 g), 4N hydrogen chloride/ethyl acetate (5 mL) and ethyl acetate (5 mL) was stirred at room temperature for 3 hr. The precipitate was collected by filtration, and the aqueous layer was basified and extracted with ethyl acetate and aqueous sodium hydroxide solution. The organic layer was washed with saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane), 0.5M succinic acid/methanol solution was added, and the solvent was evaporated under reduced pressure. The obtained residue was recrystallized from ethyl acetate-hexane to give the title compound (0.032 g, 6%) as a white powder.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. extractionextracted with ethyl acetate and aqueous sodium hydroxide solution
  3. washThe organic layer was washed with saturated brine
  4. customdried
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane), 0.5M succinic acid/methanol solution
  7. additionwas added
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-379ebbf62da94d5588fa4ae7c6a5d4ed
Source dataset
uspto-grants-2012_12
Patent number
US08329687B2

Reaction notes

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