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

HRID 1013094Notes

Reaction equation

HRID 1013094 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 ammonium hydroxide (3.5 L) and charge the solution into 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 RT. Combine the two lots and concentrate. Dissolve the residue in MTBE (3.5 L) and water (3.5 L). Adjust the pH to 6.5 using 2 N NaOH or 1 N HCl as appropriate (typically the pH is about pH=5.1 and the adjustment requires about 50 mL 2 N NaOH). Discard the organic layer, adjust the aqueous layer to pH=13 using 50% NaOH (˜150 mL). Extract with MTBE (2×3.5 L), wash the combined organic layers with brine (3.5 L), dry (sodium sulfate) and concentrate 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.

Workup

  1. customsplit the mixture into two equal lots
  2. customIn two separate runs
  3. additionadd concentrated ammonium hydroxide (3.5 L)
  4. additioncharge the solution into 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 RT
  8. concentrationconcentrate
  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 (sodium sulfate)
  13. concentrationconcentrate

Sources & evidence

ORD record
ord-9f4bd746ad7147658022e1988e141901
Source dataset
uspto-grants-2011_07
Patent number
US07981882B2

Reaction notes

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