Triethylamine → Mioflazine Hydrochloride

HRID 35339Notes

Reaction equation

HRID 35339 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:13])=[O:4].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:22][CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH:26]2[C:31]([NH2:33])=[O:32])=[CH:17][CH:16]=1.C(N(CC)CC)C>CN(C)C=O>[OH2:4].[ClH:1].[ClH:1].[NH2:33][C:31]([CH:26]1[N:25]([CH2:24][CH2:23][CH2:22][CH:21]([C:18]2[CH:17]=[CH:16][C:15]([F:14])=[CH:20][CH:19]=2)[C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:30][CH2:29][N:28]([CH2:2][C:3]([NH:5][C:6]2[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][C:7]=2[Cl:13])=[O:4])[CH2:27]1)=[O:32]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 772062-Chloro-N-(2,6-dichlorophenyl)acetamideHCID 138832881-[4,4-Bis(4-fluorophenyl)butyl]-2-piperazinecarboxamide

Product 1

HCID 21896660Mioflazine Hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4.05 parts of 2-chloro-N-(2,6-dichlorophenyl)acetamide, 5.6 parts of 1-[4,4-bis(4-fluorophenyl)butyl]-2-piperazinecarboxamide, 2.94 parts of N,N-diethylethanamine and 63 parts of N,N-dimethylformamide was stirred for 5 hours at 70° C. The reaction mixture was poured onto ice-water. The precipitated product was filtered off and dissolved in dichloromethane. The solution was washed with water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanone and 2-propanol. The salt was filtered off and stirred for 30 minutes in 1,1'-oxybisethane, yielding 4.54 parts of 3-(aminocarbonyl)-4-[4,4-bis(4-fluorophenyl)butyl]-N-(2,6-dichlorophenyl)-1-piperazineacetamide dihydrochloride monohydrate; mp. 182.7° C. (compound 72).

Workup

  1. additionThe reaction mixture was poured onto ice-water
  2. filtrationThe precipitated product was filtered off
  3. dissolutiondissolved in dichloromethane
  4. washThe solution was washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column-chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. filtrationThe salt was filtered off
  13. stirringstirred for 30 minutes in 1,1'-oxybisethane

Sources & evidence

ORD record
ord-ee4360a5bfb845cdbeffa88fa4d6812b
Source dataset
uspto-grants-1988_08
Patent number
US04766125

Reaction notes

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