Acetyl chloride → HCID 14349089, compound

HRID 346072Notes

Reaction equation

HRID 346072 reaction equation
C(O)(=O)/C=C\[C:4]([OH:6])=[O:5].COC1C(OC)=CC2C(OC3C=CC(F)=CC=3)CNCCC=2C=1.[C:32](=[O:35])([OH:34])[O-].[Na+].C(Cl)(=O)C.[C:41]([N:44]1[CH2:50][CH:49]([O:51][C:52]2[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=2)[C:48]2[CH:59]=[C:60]([O:65][CH3:66])[C:61]([O:63][CH3:64])=[CH:62][C:47]=2[CH2:46][CH2:45]1)(=O)[CH3:42].[H-].[Al+3].[Li+].[H-].[H-].[H-]>ClCCl.O1CCCC1.CCOCC>[C:4]([OH:6])(=[O:5])[C:32]([OH:34])=[O:35].[CH3:64][O:63][C:61]1[C:60]([O:65][CH3:66])=[CH:59][C:48]2[CH:49]([O:51][C:52]3[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=3)[CH2:50][N:44]([CH2:41][CH3:42])[CH2:45][CH2:46][C:47]=2[CH:62]=1

Participants

9

Reactant 5

HCID 6367Acetyl chlorideHCID 516892Sodium BicarbonateHCID 14349070HCID 14349070, compoundHCID 19991706HCID 19991706, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 14349089HCID 14349089, compoundYield 49.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7,8-dimethoxy-1-(4-fluorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine of Example 42, (4.3 g, 13.5 mmole) in 100 ml dichloromethane containing sodium bicarbonate (2.3 g, 27 mmole) was slowly added a solution of acetyl chloride (1.2 g, 15.6 mmole) in 25 ml dichloromethane. After stirring three hours at ambient temperature the reaction mixture was evaporated, stirred with water and extracted with ethyl acetate-ether. The organic extract was washed with diluted HCl, water, saturated NaCl and was dried (anhydrous MgSO4), filtered and evaporated to 4.2 g (89%) of an oil. A solution of the resultant 3-acetyl-7,8-dimethoxy-1-(4-fluorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine (4.2 g, 11.7 mmole) in 50 ml tetrahydrofuran was slowly added to a solution of lithium aluminum hydride (1M in THF, 23 mmole, 23 ml). After stirring one hour at ambient temperature the reaction mixture was diluted with anhydrous ether and quenched by slow addition of saturated ammonium chloride. The organic phase was washed with water and saturated NaCl and was dried (anhydrous MgSO4), filtered and evaporated to 4 g of an oil. This oil was converted to the oxalate salt as in Example 1 and was recrystallized from isopropanol-ether to give 2.5 g (49%) of 7,8-dimethoxy-3-ethyl-1-(4-fluorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine oxalate, d 165°-166° C.

Workup

  1. customwas evaporated
  2. stirringstirred with water
  3. extractionextracted with ethyl acetate-ether
  4. extractionThe organic extract
  5. washwas washed with diluted HCl, water, saturated NaCl
  6. dry with materialwas dried (anhydrous MgSO4)
  7. filtrationfiltered
  8. customevaporated to 4.2 g (89%) of an oil
  9. stirringAfter stirring one hour at ambient temperature the reaction mixture
  10. customquenched by slow addition of saturated ammonium chloride
  11. washThe organic phase was washed with water and saturated NaCl
  12. dry with materialwas dried (anhydrous MgSO4)
  13. filtrationfiltered
  14. customevaporated to 4 g of an oil
  15. customwas recrystallized from isopropanol-ether

Sources & evidence

ORD record
ord-01e0823a983f4d6aa94b3a7525b907c3
Source dataset
uspto-grants-1991_10
Patent number
US05059688

Reaction notes

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