Diethyl (ethoxymethylene)malonate → HCID 12778916, compound

HRID 1995311Notes

Reaction equation

HRID 1995311 reaction equation
[NH2:1][C:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]=1.C([O:11][CH:12]=[C:13]([C:19](OCC)=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15])C>C(O)C>[O:11]=[C:12]1[N:8]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[N:1][CH:19]=[C:13]1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

4

Reactant 2

HCID 6871Diethyl (ethoxymethylene)malonateHCID 97937283,4,5,6-tetrahydro-2H-azepin-7-amine

Product 1

HCID 12778916HCID 12778916, compoundYield 80.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

67.2 g of 7-amino-3,4,5,6-tetrahydro-2H-azepine are dissolved in 600 ml. of ethanol and the solution is cooled to -10° C. and to the reaction mixture a solution of 127.8 g. of diethyl ethoxy-methylene-malonate in 600 ml. of ethanol is added dropwise under stirring within 1 hour. The reaction mixture is stirred for a further hour at a temperature of -10° C. to -5° C. whereafter it is boiled for 1 hour. Ethanol is distilled off at reduced pressure. The residual yellow oil containing an about 10:1 mixture of ethyl 4-oxo-4,6,7,8-hexahydro-pyrimido[1,2-a]azepine-3-carboxylate and ethyl-2-oxo-2,6,7,8,9,10-hexadhydro-pyrimido[1,2-a]azepine-3-carboxylate is dissolved in 600 ml. of benzene and shaken out twice subsequently with 60 ml of water. The benzene soltuion is dried over anhydrous sodium sulphate and evaporated at reduced pressure. 114 g. (80.5%) ethyl 4-oxo-4,6,7,8,9,10-hexahydro-pyrimido[1,2-a]azepine-3-carboxylate are obtained melting at 82°-84° C. after recrystallization from ethyl acetate.

Workup

  1. stirringThe reaction mixture is stirred for a further hour at a temperature of -10° C. to -5° C. whereafter it
  2. waitis boiled for 1 hour
  3. distillationEthanol is distilled off at reduced pressure
  4. additionThe residual yellow oil containing
  5. additionan about 10:1 mixture of ethyl 4-oxo-4,6,7,8-hexahydro-pyrimido[1,2-a]azepine-3-carboxylate and ethyl-2-oxo-2,6,7,8,9,10-hexadhydro-pyrimido[1,2-a]azepine-3-carboxylate
  6. dissolutionis dissolved in 600 ml
  7. stirringof benzene and shaken out twice subsequently with 60 ml of water
  8. dry with materialThe benzene soltuion is dried over anhydrous sodium sulphate
  9. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-ec8d61cb58e748d3883431baa013829b
Source dataset
uspto-grants-1983_09
Patent number
US04404205

Reaction notes

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