Ethanol → 1-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane

HRID 1003992Notes

Reaction equation

HRID 1003992 reaction equation
Cl.[N:2]1([C:8]([N:10]2[CH2:16][CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[C:24](OC(=O)C)(=[O:26])[CH3:25].C(O)C>ClCCl>[C:24]([N:13]1[CH2:14][CH2:15][CH2:16][N:10]([C:8]([N:2]2[CH2:3][CH2:4][O:5][CH2:6][CH2:7]2)=[O:9])[CH2:11][CH2:12]1)(=[O:26])[CH3:25]

Participants

6

Reactant 4

HCID 702EthanolHCID 7918Acetic AnhydrideHCID 8471Triethylamine2×HCID 227070621-(4-Morpholinecarbonyl)-1,4-diazepane hydrochloride

Product 1

HCID 155382861-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepaneYield 92.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 1-(4-morpholinecarbonyl)-1,4-diazepane hydrochloride (50 g, 0.2 mol) and triethylamine (42 ml, 30.5 g, 0.3 mol) in dichloromethane (400 ml) at 5° C. was added acetic anhydride (23 ml, 24.9 g, 0.24 mol) dropwise over 15 minutes and the reaction was then stirred for a further 2 hours at room temperature under nitrogen. Dilution with dichloromethane (600 ml) was followed by washing with saturated aqueous sodium bicarbonate (2×200 ml) and the combined aqueous layers extracted with dichloromethane (1×100 ml). The dichloromethane layers were combined and washed with saturated brine, dried over MgSO4 and evaporated to give a light brown oil. This was dissolved in dichloromethane (300 ml) and treated with triethylamine (8 ml, 5.8 g, 0.06 mol) and ethanol (5 ml), stirred for 1 hour at room temperature then washed with saturated sodium bicarbonate and the aqueous layer extracted with dichloromethane (5×). The combined dichloromethane layers were dried over MgSO4 and evaporated under reduced pressure to give a yellow oil which was then azeotroped with dichloromethane (4×) to give the title compound as a yellow oil (47.1 g, 92%). Rf 0.45 (0.880 aqueous ammonia: methanol:dichloromethane 1:10:90, v/v). MS m/z 256 (MH)+. Found: C,52.62; H,8.18; N,15.02; C12H21N3O3 0.3CH2Cl2 requires C, 52.61; H, 7.75; N,14.96%.

Workup

  1. washby washing with saturated aqueous sodium bicarbonate (2×200 ml)
  2. extractionthe combined aqueous layers extracted with dichloromethane (1×100 ml)
  3. washwashed with saturated brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto give a light brown oil
  7. stirringstirred for 1 hour at room temperature
  8. washthen washed with saturated sodium bicarbonate
  9. extractionthe aqueous layer extracted with dichloromethane (5×)
  10. dry with materialThe combined dichloromethane layers were dried over MgSO4
  11. customevaporated under reduced pressure
  12. customto give a yellow oil which
  13. customwas then azeotroped with dichloromethane (4×)

Sources & evidence

ORD record
ord-f95f37261e8d45a19f18bda88f440317
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

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