Toluene → HCID 131715619, compound

HRID 580416Notes

Reaction equation

HRID 580416 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:15][C:14]3[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=3[NH:12][C:11](=[O:20])[C@H:10]2[CH3:21])=[CH:5][CH:4]=1.[H-].[Na+].[CH3:24][N:25]([CH2:27][CH2:28][Cl:29])[CH3:26].C1(C)C=CC=CC=1>CN(C)C=O>[ClH:29].[CH3:24][N:25]([CH3:26])[CH2:27][CH2:28][N:12]1[C:13]2[CH:19]=[CH:18][CH:17]=[CH:16][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]([CH3:21])[C:11]1=[O:20]

Participants

6

Reactant 4

HCID 1140TolueneHCID 79012-Chloro-N,N-dimethylethylamine2×HCID 24758Sodium hydride2×HCID 70404636HCID 70404636, compound

Product 1

HCID 131715619HCID 131715619, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (cis)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-3-methyl-2H-1-benzazepin-2-one (0.37 g, 1.32 mmol) in 13 ml of dry dimethylformamide was treated with sodium hydride (0.035 g, 1.45 mmol, room temperature, argon) and stirring at room temperature was continued for one-half hour. N,N-Dimethyl-2-chloroethylamine (0.92 ml of a 2.15M solution in toluene 1.97 mmol) was introduced and the reaction was carried out for 3 hours (85° C. oil bath). TLC indicated that reaction progress had stopped after 11/2 hours. More sodium hydride (0.02 g, 0.83 mmol) was added (room temperature) followed by more N,N-dimethyl-2-chloroethylamine solution (0.46 ml, 0.99 mmol). The reaction was continued at 85° C. (oil bath temperature) for 31/2 hours. Dimethylformamide was removed in vacuo. Ethyl acetate and water were added, the water layer was washed with ethyl acetate, the combined ethyl acetate layers were washed with water (2 times), brine, dried over sodium sulfate and evaporated in vacuo to yield 0.42 g of a yellow oil. Acidification with saturated hydrogen chloride/ether solution followed by evaporation in vacuo and subsequent trituration with ether (1 crop) yielded 0.37 g of an off-white solid. TLC of the mother liquor revealed the presence of unconsumed starting material. Recrystallization from ethyl acetate/methanol (2 crops) yielded 0.22 g of an off-white solid, melting point 211°-216° C., dec. (foaming).

Workup

  1. waitwas continued for one-half hour
  2. custom(85° C. oil bath)
  3. customTLC indicated that reaction progress
  4. custom2 hours
  5. customwas continued at 85° C.
  6. custom2 hours
  7. customDimethylformamide was removed in vacuo
  8. additionEthyl acetate and water were added
  9. washthe water layer was washed with ethyl acetate
  10. washthe combined ethyl acetate layers were washed with water (2 times), brine
  11. dry with materialdried over sodium sulfate
  12. customevaporated in vacuo

Sources & evidence

ORD record
ord-5d55d786f51c4b38b50650f3571a0424
Source dataset
uspto-grants-1988_06
Patent number
US04752645

Reaction notes

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