Ammonium Acetate → 3,4,5,6-Tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl ester

HRID 481074

Reaction equation

HRID 481074 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15](=O)[CH2:14][CH2:13][CH2:12][CH2:11][C:8]=2[NH:9][CH:10]=1)=[O:5])[CH3:2].[NH2:17][CH:18]=[CH:19][CH:20]=O.C([O-])(=O)C.[NH4+]>C(N(CC)CC)C.ClCCl.C([O-])(O)=O.[Na+]>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:15]3[N:17]=[CH:18][CH:19]=[CH:20][C:14]=3[CH2:13][CH2:12][CH2:11][C:8]=2[NH:9][CH:10]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 517165Ammonium AcetateHCID 18696565Ethyl 4-oxo-1,4,5,6,7,8-hexahydrocyclohepta[B]pyrrole-3-carboxylateHCID 539779123-Aminoacrolein

Product 1

HCID 206056123,4,5,6-Tetrahydro-3,10-diazabenzo[e]azulene-1-carboxylic acid ethyl esterYield 20%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-oxo-1,4,5,6,7,8-hexahydro-cyclohepta(b)pyrrole-3-carboxylic acid ethyl ester (7.0 g, 31.67 mmol), 3-amino-prop-2-enal (3.37 g, 47.5 mmol) and ammonium acetate (365 mg, 4.75 mmol) in triethylamine (7 mL) is heated at 110° C. for 4 h. It is cooled to room temperature and the solid residue is dissolved in 100 mL dichloromethane and 100 mL sat. NaHCO3 solution. Layers are separated and the aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL). Combined organic layers are dried (Na2SO4) and evaporated. Flash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1), provides 3,4,5,6-tetrahydro-3,10-diaza-benzo[e]azulene-1-carboxylic acid ethyl ester (1.6 g, 20%) as off-white solid. 1H NMR (400 MHz, CD3OD) δ1.247 (3H, t), 2.227 (2H, m), 2.631 (4H, m), 4.197 (2H, q), 7.170 (1H, m), 7.405 (1H, s), 7.686 (1H, d), 8.375 (1H, d). MS (ES+) 257 (M+1)

Workup

  1. temperatureIt is cooled to room temperature
  2. customLayers are separated
  3. extractionthe aqueous phase is extracted with 4:1 DCM/2-propanol (4×100 mL)
  4. dry with materialCombined organic layers are dried (Na2SO4)
  5. customevaporated
  6. washFlash Chromatography on silica gel, eluting with EtOAc:triethylamine (20:1)

Sources & evidence

ORD record
ord-a2d273c7fe884f7ab25a83f859d90c45
Source dataset
uspto-grants-2003_11
Patent number
US06653471B2

Linked notes

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