1-Chloroethyl chloroformate → HCID 19919599, compound

HRID 1648357Notes

Reaction equation

HRID 1648357 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]2[CH:11]=[CH:12][CH:13]=[C:14]([N:15]3[CH2:20][CH2:19][N:18](CC4C=CC=CC=4)[CH2:17][CH2:16]3)[C:8]=2[CH:7]=1)=[O:5])[CH3:2].[Cl:28]C(OC(Cl)C)=O>ClCCCl>[ClH:28].[N:15]1([C:14]2[C:8]3[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[S:10][C:9]=3[CH:11]=[CH:12][CH:13]=2)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 15289950HCID 15289950, compound

Product 1

HCID 19919599HCID 19919599, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve ethyl-4-[4-(phenylmethyl)-1-piperazinyl]-benzo[b]thiophene-2-carboxylate (2.00 g, 5.26 mmol, prepared in example 1) in 1,2-dichloroethane (40 mL) under an atmosphere of nitrogen and cool the solution with an ice bath. Add 1-chloroethyl chloroformate (1.40 mL, 13.1 mmol) and warm the reaction to room temperature (20° C.). Stir for 30 minutes and then heat the reaction to reflux for 4.5 hours. After cooling, concentrate under vacuum, add ethanol (40 mL) to the residue, reflux for 1.5 hours under nitrogen and then stir at room temperature for 15 hours. Concentrate under vacuum and recrystallize the residue from warm ethanol (50 mL). Collect the product by suction filtration and wash with ether to provide the title compound (1.14 g) as a white solid, mp 238°-240° C.; 1H NMR (DMSO-d6) δ 9.43 (2H, bs), 8.13 (1H, s), 7.75 (1H, d, J=8.2 Hz), 7.49 (1H, t, J=7.9 Hz), 7.06 (1H, d, J=7.5 Hz), 4.37 (2H, q, J=7.1 Hz), 3.34 (8H, bs), 1.35 (3H, t, J=7.1 Hz); 13C NMR (DMSO-d6) δ 161.90, 148.81, 142.84, 132.69, 131.91, 128.35, 128.01, 117.91, 113.64, 61.50, 48.88, 43.01, 14.17; IR (KBr) 1711, 1281, 1246, 756 cm-1 ; EI/MS (70eV) 290(55%), 248(100%). IC50 =89 nM (5HT1ABinding Affinity) IC50 =47 nM (5HT1DBinding Affinity)

Workup

  1. temperaturecool the solution with an ice bath
  2. customthe reaction to room temperature (20° C.)
  3. temperatureheat
  4. customthe reaction
  5. temperatureto reflux for 4.5 hours
  6. temperatureAfter cooling
  7. concentrationconcentrate under vacuum
  8. additionadd ethanol (40 mL) to the residue
  9. temperaturereflux for 1.5 hours under nitrogen
  10. stirringstir at room temperature for 15 hours
  11. concentrationConcentrate under vacuum
  12. customrecrystallize the residue
  13. temperaturefrom warm ethanol (50 mL)
  14. customCollect the product
  15. filtrationby suction filtration
  16. washwash with ether

Sources & evidence

ORD record
ord-0c64ba78aaf44456a863eaaa10306370
Source dataset
uspto-grants-1995_07
Patent number
US05436246

Reaction notes

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