Formaldehyde → Benzyl 2-(3-(1H-imidazol-1-YL)-1,2,4-thiadiazol-5-YL)pyrrolidine-1-carboxylate

HRID 1170515Notes

Reaction equation

HRID 1170515 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[S:20][N:19]=[C:18]([NH2:21])[N:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:22]([CH:24]=O)=O.[Cl-].[NH4+:27].P([O-])([O-])([O-])=O.[Ca+2].P([O-])([O-])([O-])=O.[Ca+2].[Ca+2].[CH2:41]=O>C(O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[S:20][N:19]=[C:18]([N:21]2[CH:24]=[CH:22][N:27]=[CH:41]2)[N:17]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 7860GlyoxalHCID 24456Tricalcium PhosphateHCID 25517Ammonium ChlorideHCID 53436030Benzyl 2-(3-amino-1,2,4-thiadiazol-5-YL)pyrrolidine-1-carboxylate

Product 1

HCID 53436029Benzyl 2-(3-(1H-imidazol-1-YL)-1,2,4-thiadiazol-5-YL)pyrrolidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-(3-Amino-[1,2,4]thiadiazol-5-yl)-pyrrolidine-1-carboxylic acid benzyl ester (9.40 g, 30.9 mmol) was dissolved in ethanol (80 mL), glyoxal (40% wt) (19.6 g, 101.4 mmol) was added to the reaction and the solution was refluxed to 3 hours. Ammonium chloride (7.80 g, 146 mmol) and calcium phosphate (11.0 g, 110 mmol) were added followed by subsequent addition of formalin (11.0 g of a 40% aqueous solution, 147 mmol) while the reaction was maintained at reflux for 16 hours. The solution was concentrated under vacuo. The crude residue was dissolved in water (20 mL) and washed with ethyl acetate (15 mL). The aqueous layer was basified to pH=9 with 1N NaOH. The aqueous layer was then extracted with ethyl acetate (2×100 mL). The organic layers were combined and concentrated under vacuo to afford 7.2 g (66%) of 2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-pyrrolidine-1-carboxylic acid benzyl ester as red oil.

Workup

  1. temperaturethe solution was refluxed to 3 hours
  2. temperaturewas maintained
  3. temperatureat reflux for 16 hours
  4. concentrationThe solution was concentrated under vacuo
  5. dissolutionThe crude residue was dissolved in water (20 mL)
  6. washwashed with ethyl acetate (15 mL)
  7. extractionThe aqueous layer was then extracted with ethyl acetate (2×100 mL)
  8. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-4bfdc6c764474df8a56cbdb402f7cd16
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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