Methyl iodide → (cis)-3-Methoxy-1-[2-(dimethylamino)ethyl]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one, monohydrochloride

HRID 1253309Notes

Reaction equation

HRID 1253309 reaction equation
[ClH:1].[OH:2][C@H:3]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH2:8][C:7]2[CH:18]=[C:19]([C:22]([F:25])([F:24])[F:23])[CH:20]=[CH:21][C:6]=2[N:5]([CH2:26][CH2:27][N:28]([CH3:30])[CH3:29])[C:4]1=[O:31].[H-].[Na+].I[CH3:35]>CN(C)C=O>[ClH:1].[CH3:35][O:2][C@H:3]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH2:8][C:7]2[CH:18]=[C:19]([C:22]([F:23])([F:25])[F:24])[CH:20]=[CH:21][C:6]=2[N:5]([CH2:26][CH2:27][N:28]([CH3:30])[CH3:29])[C:4]1=[O:31]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 131715557(cis)-3-(Hydroxy)-1-[2-(dimethylamino)ethyl]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-7-(trifluormethyl)-2H-1-benzazepin-2-one, monohydrochloride

Product 1

HCID 131715562(cis)-3-Methoxy-1-[2-(dimethylamino)ethyl]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one, monohydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (cis)-3-(hydroxy)-1-[2-(dimethylamino)ethyl]-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-7-(trifluoromethyl)-2H-1-benzazepin-2-one, monohydrochloride (0.81 g, 1.92 mmol) in 21 ml of dimethylformamide was treated with sodium hydride (0.23 g, 5.76 mmol of a 60% mineral oil dispersion) at room temperature under argon. Stirring was continued for 30 minutes. The temperature was lowered to 0° C., iodomethane was added (0.13 ml, 2.11 mmol) and the reaction was continued for 11/2 hours at 0° C. The reaction was quenched at 0° C. with water. Dimethylformamide and water were removed in vacuo. Hexane and 1M hydrochloric acid were added, the aqueous layer was washed twice with hexane, made basic with saturated aqueous potassium carbonate solution and washed three times with ethyl acetate. The ethyl acetate layers were washed with brine, dried over sodium sulfate, and evaporated in vacuo to yield 0.95 g of an oil. This material was dissolved in a minimal amount of chloroform, treated with saturated hydrogen chloride-ether solution, evaporated in vacuo and triturated with ether/ethyl acetate/methanol (80:15:5) to yield 0.67 g of a white solid, melting point 148° C. (dec).

Workup

  1. customwas lowered to 0° C.
  2. custom2 hours
  3. customat 0° C
  4. customThe reaction was quenched at 0° C. with water
  5. customDimethylformamide and water were removed in vacuo
  6. additionHexane and 1M hydrochloric acid were added
  7. washthe aqueous layer was washed twice with hexane
  8. washwashed three times with ethyl acetate
  9. washThe ethyl acetate layers were washed with brine
  10. dry with materialdried over sodium sulfate
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-361d362197134d2faa715beef342ed88
Source dataset
uspto-grants-1988_05
Patent number
US04748239

Reaction notes

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