1-Chloroethyl chloroformate → HCID 86751336, compound

HRID 1418588Notes

Reaction equation

HRID 1418588 reaction equation
[S:1]1[CH:5]=[C:4]([CH2:6][C@@H:7]2[CH2:12][N:11](CC3C=CC=CC=3)[CH2:10][CH2:9][N:8]2[C:20](=[O:35])[C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[C:3]2[CH:36]=[CH:37][CH:38]=[CH:39][C:2]1=2.[Cl:40]C(OC(Cl)C)=O>ClCCl>[ClH:40].[S:1]1[CH:5]=[C:4]([CH2:6][C@@H:7]2[CH2:12][NH:11][CH2:10][CH2:9][N:8]2[C:20](=[O:35])[C:21]2[CH:22]=[C:23]([C:31]([F:32])([F:33])[F:34])[CH:24]=[C:25]([C:27]([F:30])([F:28])[F:29])[CH:26]=2)[C:3]2[CH:36]=[CH:37][CH:38]=[CH:39][C:2]1=2

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 86751338HCID 86751338, compound

Product 1

HCID 86751336HCID 86751336, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2R)-2-(benzo[b]thiophen-3-yl-methyl)-4-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]-piperazine (0.75 g) in dichloromethane (8 ml) was added dropwise 1-chloroethyl chloroformate (0.19 ml) at ice-bath temperature. The resulting mixture was stirred at room temperature for 1 hour and then at reflux temperature for 5 hours. The reaction mixture was evaporated under reduced pressure. Methanol (5 ml) was added to the residue and the whole mixture was heated under refluxing for 1 hour. The mixture was concentrated in vacuo and the residue was partitioned between aqueous sodium bicarbonate solution (10 ml) and ethyl acetate (20 ml). The organic layer was separated, washed with brine and dried over magnesium sulfate. After evaporation of the solvent in vacuo, the residue was treated with 4N hydrogen chloride in ethyl acetate solution to afford (2R)-2-(benzo[b]thiophen-3-yl-methyl)-1-[3,5-bis(trifluoromethyl)benzoyl]piperazine hydrochloride (0.69 g).

Workup

  1. temperatureat reflux temperature for 5 hours
  2. customThe reaction mixture was evaporated under reduced pressure
  3. additionMethanol (5 ml) was added to the residue
  4. temperaturethe whole mixture was heated
  5. temperatureunder refluxing for 1 hour
  6. concentrationThe mixture was concentrated in vacuo
  7. customthe residue was partitioned between aqueous sodium bicarbonate solution (10 ml) and ethyl acetate (20 ml)
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over magnesium sulfate
  11. customAfter evaporation of the solvent in vacuo
  12. additionthe residue was treated with 4N hydrogen chloride in ethyl acetate solution

Sources & evidence

ORD record
ord-69de976023e54b87ba8b5f340eb2f301
Source dataset
uspto-grants-1999_03
Patent number
US05883098

Reaction notes

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