Triethylamine → 4-[4,4-bis(4-fluorophenyl)butyl]-N-(2-chloro-6-methylphenyl)-3-(hydroxymethyl)-1-piperazineacetamide

HRID 35337Notes

Reaction equation

HRID 35337 reaction equation
I[CH2:2][CH2:3][CH2:4][CH:5]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[C:22]=1[NH:28][C:29](=[O:39])[CH2:30][N:31]1[CH2:36][CH2:35][NH:34][CH:33]([CH2:37][OH:38])[CH2:32]1.C(N(CC)CC)C>CN(C)C=O>[F:12][C:9]1[CH:10]=[CH:11][C:6]([CH:5]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:4][CH2:3][CH2:2][N:34]2[CH2:35][CH2:36][N:31]([CH2:30][C:29]([NH:28][C:22]3[C:23]([CH3:27])=[CH:24][CH:25]=[CH:26][C:21]=3[Cl:20])=[O:39])[CH2:32][CH:33]2[CH2:37][OH:38])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1039681,1'-(4-Iodobutylidene)bis[4-fluorobenzene]HCID 14230241N-(2-chloro-6-methylphenyl)-3-(hydroxymethyl)-1-piperazineacetamide

Product 1

HCID 142301644-[4,4-bis(4-fluorophenyl)butyl]-N-(2-chloro-6-methylphenyl)-3-(hydroxymethyl)-1-piperazineacetamideYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 7.4 parts of 1,1'-(4-iodobutylidene)bis[4-fluorobenzene], 5.5 parts of N-(2-chloro-6-methylphenyl)-3-(hydroxymethyl)-1-piperazineacetamide, 4.0 parts of N,N-diethylethanamine and 68 parts of N,N-dimethylformamide was stirred for 4 hours at about 70° C. The reaction mixture was cooled overnight to room temperature and the solvent was evaporated. The residue was taken up in trichloromethane. The organic phase was washed with water, dried, filtered and evaporated. The oily 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 oily residue solidified on triturating in 2,2'-oxybispropane. The product was filtered off and dried, yielding 3.21 parts (33.1%) of 4-[4,4-bis(4-fluorophenyl)butyl]-N-(2-chloro-6-methylphenyl)-3-(hydroxymethyl)-1-piperazineacetamide; mp. 149.8° C. (compound 51).

Workup

  1. temperatureThe reaction mixture was cooled overnight to room temperature
  2. customthe solvent was evaporated
  3. washThe organic phase was washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe oily residue was purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customon triturating in 2,2'-oxybispropane
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-fb8339a2d5f447b5b43b42fa6034f67b
Source dataset
uspto-grants-1988_08
Patent number
US04766125

Reaction notes

Loading…