Water → 1-(3,4-Dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-3-benzazepine oxalate

HRID 2107715Notes

Reaction equation

HRID 2107715 reaction equation
[CH3:1][O:2][C:3]1[C:14]([O:15][CH3:16])=[CH:13][C:6]2[CH:7]([OH:12])[CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1.[H-].[Na+].[Cl:19][C:20]1[CH:21]=[C:22](F)[CH:23]=[CH:24][C:25]=1[Cl:26].[OH2:28].CN(C)C=[O:32]>>[C:14]([OH:15])(=[O:32])[C:3]([OH:2])=[O:28].[Cl:19][C:20]1[CH:21]=[C:22]([CH:23]=[CH:24][C:25]=1[Cl:26])[O:12][CH:7]1[C:6]2[CH:13]=[C:14]([O:15][CH3:16])[C:3]([O:2][CH3:1])=[CH:4][C:5]=2[CH2:11][CH2:10][NH:9][CH2:8]1

Participants

6

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 740281,2-Dichloro-4-fluorobenzeneHCID 13118512HCID 13118512, compound

Product 1

HCID 143491131-(3,4-Dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-3-benzazepine oxalateYield 57%

Conditions

Temperature
60 °C

Procedure

A solution of 7,8-dimethoxy-1-hydroxy-2,3,4,5-tetrahydro-3-benzazepine (3 g, 13.4 mmole) in 25 ml dimethylformamide was slowly dropped into a stirring suspension of sodium hydride (50% oil dispersion, 0.7 g, 14.8 mmole), previously washed with hexane, in 10 ml dimethylformamide. After the addition was completed, the mixture was warmed for one hour at 60° C., then was cooled and a solution of 3,4-dichlorofluorobenzene (2.4 g, 14.8 mmole) in 10 ml dimethylformamide was added. After stirring two hours at ambient temperature, the reaction mixture was stirred with 400 ml water and was extracted with ethyl acetate. The organic extract was washed with ethyl acetate. The organic extract was washed with water and saturated NaCl and was dried (anhydrous MgSO4), filtered and evaporated to 7 g of an oil. This oil was purified by HPLC (silica gel, 5% methanol in dichloromethane) to give 2.8 g (57%) of an oil. This oil was converted to the oxalate salt as in Example 1 and was recrystallized from ethyl acetate-methanol to give 2.1 g (34%) of 1,(3-4-dichlorophenoxy)-7,8-dimethoxy-2,3,4,5-tetrahydro-3-benzazepine oxalate, d 167°-168° C.

Workup

  1. washpreviously washed with hexane, in 10 ml dimethylformamide
  2. additionAfter the addition
  3. temperaturewas cooled
  4. extractionwas extracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with ethyl acetate
  7. extractionThe organic extract
  8. washwas washed with water and saturated NaCl
  9. dry with materialwas dried (anhydrous MgSO4)
  10. filtrationfiltered
  11. customevaporated to 7 g of an oil
  12. customThis oil was purified by HPLC (silica gel, 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-8f33fa8c9f714a94a7cf119c339b49ef
Source dataset
uspto-grants-1990_06
Patent number
US04935418

Reaction notes

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