1-Chloroethyl chloroformate → 7-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride

HRID 492412Notes

Reaction equation

HRID 492412 reaction equation
[Cl:1][C:2]([O:4][CH:5](Cl)[CH3:6])=O.CO[CH:10]1[C:16]2[CH:17]=CC=[CH:20][C:15]=2[CH2:14][CH2:13][N:12](C)[CH2:11]1>ClCCCl>[ClH:1].[CH3:2][O:4][C:5]1[CH:6]=[CH:17][C:16]2[CH2:10][CH2:11][NH:12][CH2:13][CH2:14][C:15]=2[CH:20]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 68748342methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 212429067-methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochlorideYield 179%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

The reactions are set up in a 22 L flask, each equipped with a mechanical stirrer, heating mantle, condenser and nitrogen bubbler. Add 1-chloroethyl chloroformate (620 mL, 5.750 mol, 10.0 eq) over 1 hour to methoxy-3-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (110 g, 575 mmol, 1.0 eq) dissolved in 1,2-dichloroethane (8.0 L) at 60° C. under nitrogen, in a 22 L flask. The solution turns dark purple over the next 2 hours. Heat the mixture to reflux and stir for 16 hours under nitrogen. The reaction is determined to be complete by TLC. Cool the reaction flask and concentrate under vacuum to an oil. Dissolve the oil in methanol (4 L) and add to a 22 L reaction flask and stir for 16 hours at room temperature under nitrogen. Concentrate the resulting solution under vacuum to an off-white solid 220 g, 90% yield).

Workup

  1. customThe reactions are set up in a 22 L flask
  2. customeach equipped with a mechanical stirrer
  3. temperatureheating mantle, condenser and nitrogen bubbler
  4. customturns dark purple over the next 2 hours
  5. temperatureHeat the mixture
  6. temperatureto reflux
  7. temperatureCool the reaction flask
  8. concentrationconcentrate under vacuum to an oil
  9. dissolutionDissolve the oil in methanol (4 L)
  10. additionadd to a 22 L reaction flask
  11. stirringstir for 16 hours at room temperature under nitrogen

Sources & evidence

ORD record
ord-41248d370a3846998acd2747a8476014
Source dataset
uspto-grants-2009_05
Patent number
US07531557B2

Reaction notes

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