1-Piperazinecarboxylic acid, ethyl ester → 4-(5-Fluorobenzofuran-3-yl)-piperazine-1-carboxylic acid ethyl ester

HRID 2241972Notes

Reaction equation

HRID 2241972 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH2:8][C:7](=O)[C:6]=2[CH:11]=1.[CH2:12]([O:14][C:15]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)=[O:16])[CH3:13]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:12]([O:14][C:15]([N:17]1[CH2:18][CH2:19][N:20]([C:7]2[C:6]3[CH:11]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[O:9][CH:8]=2)[CH2:21][CH2:22]1)=[O:16])[CH3:13]

Participants

5

Reactant 2

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 130130565-Fluoro-1-benzofuran-3(2H)-one

Product 1

HCID 592048394-(5-Fluorobenzofuran-3-yl)-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of TiCl4 (1M solution in CH2Cl2, 7 ml) and 5-fluoro-benzofuran -3-one (Cagniant, et al., Comptus Rendus des Seances Acad. de Sci., Ser. C, 282:993 (1976), 3.0 g) (3.0 g, 19.7 mmol) in methylene chloride (200 ml) at −10° C., ethyl-1-piperizine carboxylate (commercially available) (3.9 g, 35 mmol) was slowly added. After the addition, the reaction mixture was warmed to room temperature and slowly refluxed for 24 hours. After cooling to room temperature, the reaction was quenched with 2 N aqueous HCl. The organic layer was separated and the aqueous layer was extracted with chloroform. The combined organic layers were washed well with water and dried over anhydrous MgSO4, then filtered and concentrated resulting in a brown oil. Yield: 3.5 g, (60%); MS (ESI) m/z 293 [M+−H]+.

Workup

  1. additionAfter the addition
  2. temperatureslowly refluxed for 24 hours
  3. temperatureAfter cooling to room temperature
  4. customthe reaction was quenched with 2 N aqueous HCl
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with chloroform
  7. washThe combined organic layers were washed well with water
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customresulting in a brown oil

Sources & evidence

ORD record
ord-bc2b2b0e81fd43a2b9221e27b4a256fb
Source dataset
uspto-grants-2010_03
Patent number
US07671056B2

Reaction notes

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