Hydrochloric Acid → N-Boc-hexahydro-1H-azepin-4-one

HRID 541444Notes

Reaction equation

HRID 541444 reaction equation
[O:1]=[C:2]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4][CH:3]1C(OCC)=O.[OH-].[Na+].Cl>O1CCOCC1.O>[O:1]=[C:2]1[CH2:3][CH2:4][CH2:5][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 44365701-tert-Butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate

Product 1

HCID 1512679N-Boc-hexahydro-1H-azepin-4-oneYield 77.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution 1-tert-butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate (429.1, 19.0 g, 66.6 mmol, 1.00 equiv) in 1,4-dioxane (190 mL) was added dropwise sodium hydroxide (4.00 g, 100 mmol, 1.50 equiv) in water (100 mL). The resulting mixture was stiffed at room temperature overnight. The pH was then adjusted to 4-5 with hydrogen chloride (aq. 3 M) and the resulting solution was extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 2×10 mL of brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography using ethyl acetate/petroleum ether (1:3) as eluent to furnish 11.0 g (77%) of the title compound as a yellow oil.

Workup

  1. extractionthe resulting solution was extracted with 2×50 mL of ethyl acetate
  2. washThe combined organic layers were washed with 2×10 mL of brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-9588abffc821431aa5d5bff5914222c1
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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