Hydrochloric Acid → 7-bromo-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one

HRID 236144Notes

Reaction equation

HRID 236144 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[CH:6][C:7]([O:13][CH:14]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15]2)=[C:8]([CH:12]=1)[C:9](N)=[O:10].Cl.S(Cl)([Cl:23])=O.C(N(CC)CC)C>O>[Br:3][C:4]1[CH:5]=[CH:6][C:7]2[O:13][CH:14]([CH2:18][CH2:17][Cl:23])[CH2:15][N:16]([CH3:19])[C:9](=[O:10])[C:8]=2[CH:12]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 137262855-Bromo-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide

Product 1

HCID 137262957-bromo-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)oneYield 60.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 9.6 g (0.24 mole) of sodium hydroxide in 200 ml of water was added 37 g (0.12 mole) of 5-bromo-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide and the mixture was heated at reflux for 18 hr. The pH of the mixture was adjusted to 6.7 with concentrated hydrochloric acid solution. The solution was concentrated under reduced pressure and the residue was boiled in 250 ml of isopropyl alcohol for 1 hr. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in chloroform and to the solution was added 28.3 g (0.24 mole) of thionyl chloride. The mixture was heated at reflux for 0.5 hr and cooled to 15° C. with an ice bath. To the mixture was added dropwise 26.6 g (0.26 mole) of triethylamine at such a rate that the temperature did not exceed 25° C. The reaction mixture was stirred at room temperature for 1 hr, then washed consecutively with 3N hydrochloric acid, 15% aqueous sodium hydroxide and water. The chloroform layer was dried over magnesium sulfate and concentrated under reduced pressure to give 23 g (60%) of brown solid. A portion of the solid was recrystallized from ethyl acetate-isopropyl ether, m.p. 92°-94° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 18 hr
  3. concentrationThe solution was concentrated under reduced pressure
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe residue was dissolved in chloroform and to the solution
  7. temperatureThe mixture was heated
  8. temperatureat reflux for 0.5 hr
  9. customdid not exceed 25° C
  10. washwashed consecutively with 3N hydrochloric acid, 15% aqueous sodium hydroxide and water
  11. dry with materialThe chloroform layer was dried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a9e6511e140b4c05b2ac1d3e4f31c49b
Source dataset
uspto-grants-1987_02
Patent number
US04642343

Reaction notes

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