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Morpholine → 6-(4-morpholinyl)-3-[3-(trifluoromethyl)phenyl]-1,5(6H)-pyridazindicarboxylic acid diethyl ester

HRID 52769
Notes
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Reaction equation

HRID 52769 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[C:2]#[CH:3].[NH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.[CH2:23]([O:25][C:26]([NH:28][N:29]=[C:30]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=1)[CH:31](Cl)Cl)=[O:27])[CH3:24]>C(Cl)Cl>[CH2:23]([O:25][C:26]([N:28]1[CH:3]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:2]([C:1]([O:5][CH2:6][CH3:7])=[O:4])=[CH:31][C:30]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)=[N:29]1)=[O:27])[CH3:24]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 8083MorpholineHCID 12182Ethyl propiolateHCID 81531DiisopropylethylamineHCID 53937192[2,2-Dichloro-1-[3-(trifluoromethyl)phenyl]ethylidene]hydrazinecarboxylic acid ethyl ester

Product 1

HCID 117980206-(4-morpholinyl)-3-[3-(trifluoromethyl)phenyl]-1,5(6H)-pyridazindicarboxylic acid diethyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Ethyl propiolate (3.43 g, 0.035 mole) was stirred under N2 in methylene chloride (300 mL) at RT while morpholine (3.05 g, 0.035 mole) was added dropwise over 15 min. The mixture was then refluxed for 30 min. and then cooled to room temperature (RT). Diisopropylethylamine (5.65 g, 0.0437 mole) was then added to the mixture followed by the addition of [2,2-dichloro-1-[3-(trifluoromethyl)phenyl]ethylidene]hydrazinecarboxylic acid ethyl ester (10 g, 0.029 mole) which was added dropwise as a solution in methylene chloride (60 mL) over 30 min. The mixture was then refluxed for 18 h, cooled, and partitioned 2 times with water. The organic layer was dried (MgSO4), filtered and evaporated in vacuo to give a crude solid. This solid was recrystallized from cyclohexane/ethyl acetate to give 6-(4-morpholinyl)-3-[3-(trifluoromethyl)phenyl]-1,5(6H)-pyridazindicarboxylic acid diethyl ester (7.26 g, 55% yield) as a yellow solid, mp=128°-129° C.

Workup

  1. additionwas added dropwise over 15 min
  2. temperatureThe mixture was then refluxed for 30 min.
  3. temperatureThe mixture was then refluxed for 18 h
  4. temperaturecooled
  5. custompartitioned 2 times with water
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto give a crude solid
  10. customThis solid was recrystallized from cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-31b587679ba9448b8747dc7f4228e667
Source dataset
uspto-grants-1997_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05616789

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes