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

HRID 247274Notes

Reaction equation

HRID 247274 reaction equation
[OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([O:14][CH:15]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16]2)=[C:9]([CH:13]=1)[C:10](N)=[O:11].Cl.S(Cl)([Cl:24])=O.C(N(CC)CC)C>O>[Cl:24][CH2:18][CH2:19][CH:15]1[CH2:16][N:17]([CH3:20])[C:10](=[O:11])[C:9]2[CH:13]=[C:5]([O:4][CH3:3])[CH:6]=[CH:7][C:8]=2[O:14]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 137262875-Methoxy-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide

Product 1

HCID 137262972-(2-Chloroethyl)-2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5(4H)-oneYield 23.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 19.2 g (0.48 mole) of sodium hydroxide in 500 ml of water was added 60 g (0.24 mole) of 5-methoxy-2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide and the mixture was heated at reflux for 24 hr. The reaction mixture was cooled and the pH adjusted to 6.8 with concentrated hydrochloric acid. The mixture was concentrated under reduced pressure and the residue was boiled in isopropyl alcohol for 1 hour. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in 500 ml of chloroform and to this solution was added 114 g (0.96 mole) of thionyl chloride. The mixture was heated at reflux for 48 hr, then cooled with an ice/acetone bath. To the mixture was added dropwise 97 g (0.96 mole) of triethylamine at such a rate that the temperature did not exceed 25° C. The reaction solution was washed in sequence with water, 3N hydrochloric acid solution, water, 15% aqueous sodium hydroxide and water and finally dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give a black solid. The solid was purified on a silica gel column using ethyl acetate as the eluting solvent to give on isolation 15 g (23%) of beige colored product, m.p. 98°-100° C.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 24 hr
  3. temperatureThe reaction mixture was cooled
  4. concentrationThe mixture was concentrated under reduced pressure
  5. filtrationThe mixture was filtered
  6. concentrationthe filtrate was concentrated
  7. dissolutionThe residue was dissolved in 500 ml of chloroform and to this solution
  8. temperatureThe mixture was heated
  9. temperatureat reflux for 48 hr
  10. temperaturecooled with an ice/acetone bath
  11. customdid not exceed 25° C
  12. washThe reaction solution was washed in sequence with water, 3N hydrochloric acid solution, water, 15% aqueous sodium hydroxide and water
  13. dry with materialfinally dried over magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customto give a black solid
  16. customThe solid was purified on a silica gel column

Sources & evidence

ORD record
ord-5d0aff8fd99f497ab37533c9f32c418f
Source dataset
uspto-grants-1987_11
Patent number
US04705853

Reaction notes

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