Formaldehyde → HCID 19817616, compound

HRID 1086996Notes

Reaction equation

HRID 1086996 reaction equation
C([N:4]1[C:8](=[O:9])[CH2:7][S:6][CH2:5]1)C#C.[CH2:10]=[O:11].Cl.FC1C=CC(C(C2CCNCC2)=O)=CC=1.CCCCCC.[C:34]([O:37]CC)(=[O:36])C>C(N(CC)CC)C.O1CCOCC1.ClCCl>[C:34]([OH:37])(=[O:36])[C:10]([OH:9])=[O:11].[O:9]=[C:8]1[CH2:7][S:6][CH2:5][NH:4]1

Participants

9

Reactant 5

HCID 712FormaldehydeHCID 8058HexaneHCID 8857Ethyl AcetateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 15007143HCID 15007143, compound

Product 1

HCID 19817616HCID 19817616, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-propargyl-4-oxothiazolidine (5.02 g), paraformaldehyde (1.28 g) and 4-(4-fluorobenzoyl)-piperidine hydrochloride (10.36 g) in triethylamine (7.20 g) and approximately 20 ml sieve-dried dioxane was added 1.06 of cuprous opper chloride. The reaction flask was equipped with a reflux condenser and heated to 80° C. After 3 hours no starting material remained as observed by TLC (1:1, hexane:ethyl acetate). The reaction mixture was cooled to room temperature, diluted with dichloromethane, filtered, and concentrated in vacuo. The residue was taken up in dichloromethane and extracted with acidic aqueous medium. The combined aqueous fractions were basified by addition of Na2CO3 and extracted with dichloromethane. Combined dichloromethane fractions were dried (MgSO4), filtered, and concentrated in vacuo. The residue was dissolved in ethyl acetate and filtered. The oxalate salt was precipitated from ethyl acetate and recrystallized from methanol/ethyl acetate and methanol/toluene to yield 2.34 g of 3-(4-4-(4-fluorobenzoyl)piperidino)-2-butynyl)-4-oxothiazolidine oxalate, m.p. 128.5°-129.5° C.

Workup

  1. customThe reaction flask was equipped with a reflux condenser
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. extractionextracted with acidic aqueous medium
  6. additionThe combined aqueous fractions were basified by addition of Na2CO3
  7. extractionextracted with dichloromethane
  8. dry with materialCombined dichloromethane fractions were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. filtrationfiltered
  13. customThe oxalate salt was precipitated from ethyl acetate
  14. customrecrystallized from methanol/ethyl acetate and methanol/toluene

Sources & evidence

ORD record
ord-081500be492543a091ca2677de1b5d72
Source dataset
uspto-grants-1991_07
Patent number
US05034392

Reaction notes

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