Triethylamine → Lomerizine Hydrochloride

HRID 977927

Reaction equation

HRID 977927 reaction equation
[ClH:1].Cl.[CH3:3][O:4][C:5]1[C:17]([O:18][CH3:19])=[C:16]([O:20][CH3:21])[CH:15]=[CH:14][C:6]=1[CH2:7][N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]([Cl:37])[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[CH:25][CH:24]=1.C(N(CC)CC)C>C1(C)C(C)=CC=CC=1>[ClH:37].[ClH:1].[CH3:3][O:4][C:5]1[C:17]([O:18][CH3:19])=[C:16]([O:20][CH3:21])[CH:15]=[CH:14][C:6]=1[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([CH:29]([C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 83201Trimetazidine DihydrochlorideHCID 27237731,1'-(Chloromethylene)bis(4-fluorobenzene)

Product 1

HCID 122125Lomerizine HydrochlorideYield 22.1%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

2.4 g (7.1 millimoles) of 2,3,4-trimethoxybenzylpiperazine dihydrochloride, 1.8 g (7.5 millimoles) of bis(4-fluorophenyl)methyl chloride [see J. Chem. Soc. Perkin II, 1051 (1977)] and 5.0 ml (36 millimoles) of triethylamine were heated under reflux for 9 hours in 80 ml of xylene. The reaction mixture was allowed to cool to room temprature, washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. A mixture of 2 ml of conc. hydrochloric acid and 20 ml of ethanol was added to the resulting oily product, and the mixture was concentrated under reduced pressure. Ether was added, and the precipitated crystals were collected by filtration. Recrystallization of the crystals from ethanol-ether gave 0.85 g of 1-(2,3,4-trimethoxybenzyl)-4-[bis(4-fluorophenyl)methyl]piperazine dihydrochloride. The product showed the same property values as the compound obtained in Example 4.

Workup

  1. temperatureto cool to room temprature
  2. washwashed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. additionA mixture of 2 ml of conc. hydrochloric acid and 20 ml of ethanol
  6. additionwas added to the resulting oily product
  7. concentrationthe mixture was concentrated under reduced pressure
  8. additionEther was added
  9. filtrationthe precipitated crystals were collected by filtration
  10. customRecrystallization of the crystals from ethanol-ether

Sources & evidence

ORD record
ord-a4e6364165b44ee2a74c0e6e9f851403
Source dataset
uspto-grants-1987_05
Patent number
US04663325

Linked notes

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