Hydrochloric Acid → HCID 131715618, compound

HRID 580411Notes

Reaction equation

HRID 580411 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:15][C:14]3[C:16]([C:20]([F:23])([F:22])[F:21])=[CH:17][CH:18]=[CH:19][C:13]=3[NH:12][C:11](=[O:24])[CH:10]2[CH2:25][CH2:26][CH3:27])=[CH:5][CH:4]=1.C(=O)(O)[O-].[K+].[I-].[K+].[CH3:35][N:36]([CH3:40])[CH2:37][CH2:38][Cl:39].Cl>CC(CC)=O.C1(C)C=CC=CC=1>[ClH:39].[CH3:35][N:36]([CH3:40])[CH2:37][CH2:38][N:12]1[C:13]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:21])([F:22])[F:23])[C:14]=2[CH2:15][C@H:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C@H:10]([CH2:25][CH2:26][CH3:27])[C:11]1=[O:24]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 79012-Chloro-N,N-dimethylethylamineHCID 516893Potassium BicarbonateHCID 15612111HCID 15612111, compound

Product 1

HCID 131715618HCID 131715618, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

To 1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-3-propyl-6-(trifluoromethyl)-2H-1-benzazepin-2-one (4.23 g; 11.21 mmole), potassium bicarbonate (4.49 g; 44.8 mmole; 4 eq.), and potassium iodide (catalytic amount) suspended in methylethyl ketone (70 ml) was added a 2.15M solution of 2-dimethylaminoethyl chloride (12.6 ml; 27.0 mmole; 2.4 eq.) in toluene with stirring. The mixture was refluxed for 10.5 hours, then concentrated. The residue as dissolved into ethyl acetate and washed with water. The organic layer was dried (magnesium sulfate) and concentrated. The residue was flash chromatographed (silica gel column/0.5% methanol:dichloromethane followed by 2.0% methanol:dichloromethane) and appropriate fractions were combined and concentrated. The residue was dissolved in ether and hydrogen chloride saturated ether was added. The mixture was concentrated, and coevaporated with ether several times. The solid was partitioned between ether and 1N sodium bicarbonate. The ether layer was dried (magnesium sulfate) and concentrated. After standing overnight, the solid residue was much less soluble in ether. The solid was triturated in ether and the mixture was centrifuged and a solid was obtained. Conversion to the hydrochloride salt using hydrogen chloride saturated ether yielded the title compound, melting point 180.5°-182.5° C.

Workup

  1. temperatureThe mixture was refluxed for 10.5 hours
  2. concentrationconcentrated
  3. dissolutionThe residue as dissolved into ethyl acetate
  4. washwashed with water
  5. dry with materialThe organic layer was dried (magnesium sulfate)
  6. concentrationconcentrated
  7. customchromatographed (silica gel column/0.5% methanol:dichloromethane followed by 2.0% methanol:dichloromethane) and appropriate fractions
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in ether
  10. additionhydrogen chloride saturated ether was added
  11. concentrationThe mixture was concentrated
  12. customThe solid was partitioned between ether and 1N sodium bicarbonate
  13. dry with materialThe ether layer was dried (magnesium sulfate)
  14. concentrationconcentrated
  15. customThe solid was triturated in ether
  16. customa solid was obtained

Sources & evidence

ORD record
ord-c7c07fa941f147a7af15f739d38c3dab
Source dataset
uspto-grants-1988_06
Patent number
US04752645

Reaction notes

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