Acetonitrile → 6-Methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 1965954Notes

Reaction equation

HRID 1965954 reaction equation
CS(O[CH2:6][CH2:7][C:8]1[C:13]([CH2:14][CH2:15]OS(C)(=O)=O)=[CH:12][CH:11]=[CH:10][C:9]=1[O:21][CH3:22])(=O)=O.C(#[N:25])C>>[CH3:22][O:21][C:9]1[C:8]2[CH2:7][CH2:6][NH:25][CH2:15][CH2:14][C:13]=2[CH:12]=[CH:11][CH:10]=1

Participants

3

Reactant 2

HCID 6342AcetonitrileHCID 57458019HCID 57458019, compound

Product 1

HCID 138533586-Methoxy-2,3,4,5-tetrahydro-1H-3-benzazepine

Conditions

Temperature
100 °C

Procedure

Dissolve 2,3-bis-(2-methanesulfonyloxyethyl)-1-methoxybenzene (474.4 g, 1.346 mol) in acetonitrile (7 L) and split the mixture into two equal lots. In two separate runs, add concentrated aqueous NH4OH (3.5 L) and charge the solution to a pressure vessel (PARR apparatus). Heat the solution in a closed reactor to 100° C. over 20 min (internal pressure reaches about 100 psi), and maintain at 100° C. until the reaction is complete (about 1 h, HPLC monitored). Cool the reaction mixture to ambient temperature. Combine the two lots and remove the solvent in vacuo. Dissolve the residue in MTBE (3.5 L) and water (3.5 L). Adjust the pH to 6.5 using 2M aqueous NaOH or 1M aqueous HCl as appropriate (typically the pH is about pH=5.1 and the adjustment requires about 50 mL 2M aqueous NaOH). Discard the organic layer, adjust the aqueous layer to pH=13 using 50% NaOH (about 150 mL). Extract with MTBE (2×3.5 L), wash the combined organic layers with brine (3.5 L), dry over Na2SO4, filter and concentrate in vacuo to give the title compound as a crude yellow oil that solidifies upon standing (179.3 g). Use the material for the next step without further purification. Prepare an analytical sample by purification by two Kugelrohr distillations to give a clear oil that solidifies upon standing, mp 44.3-45.0° C. 13C NMR (300 MHz, DMSO-d6), δ 156.1, 144.4, 130.3, 126.2, 121.5, 108.9, 55.5, 48.2, 47.9, 39.9, 29.1; MS (ES+) m/z 163 (M+H)+; Anal. Calc'd for C11H15NO: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.28; H, 8.62; N, 7.86.

Workup

  1. customsplit the mixture into two equal lots
  2. customIn two separate runs
  3. additionadd concentrated aqueous NH4OH (3.5 L)
  4. additioncharge the solution to a pressure vessel (PARR apparatus)
  5. temperaturemaintain at 100° C. until the reaction
  6. custom(about 1 h, HPLC monitored)
  7. temperatureCool the reaction mixture to ambient temperature
  8. customremove the solvent in vacuo
  9. dissolutionDissolve the residue in MTBE (3.5 L)
  10. extractionExtract with MTBE (2×3.5 L)
  11. washwash the combined organic layers with brine (3.5 L)
  12. dry with materialdry over Na2SO4
  13. filtrationfilter
  14. concentrationconcentrate in vacuo

Sources & evidence

ORD record
ord-9d2d68739ea64b6ea59a9b7b08328218
Source dataset
uspto-grants-2013_04
Patent number
US08420631B2

Reaction notes

Loading…