Methyl Isobutyl Ketone → 2-[[1-[3-(4-fluorophenoxy)propyl]-4-piperidinyl]methyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole ethanedioate

HRID 2309633Notes

Reaction equation

HRID 2309633 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH2:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[CH:4][CH:3]=1.[C:25](=[O:28])([O-:27])[O-].[Na+].[Na+].CC(C)C[C:34](=[O:36])C.Cl[CH2:39][CH2:40][CH2:41][O:42][C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=1>O>[C:34]([OH:36])(=[O:42])[C:25]([OH:27])=[O:28].[F:49][C:46]1[CH:47]=[CH:48][C:43]([O:42][CH2:41][CH2:40][CH2:39][N:22]2[CH2:21][CH2:20][CH:19]([CH2:18][C:10]3[N:9]([CH2:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=4[N:11]=3)[CH2:24][CH2:23]2)=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 743911-(3-Chloropropoxy)-4-fluorobenzeneHCID 140128661-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-1H-benzimidazole

Product 1

HCID 1317152632-[[1-[3-(4-fluorophenoxy)propyl]-4-piperidinyl]methyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole ethanedioateYield 53%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 6.5 parts of 1-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-1H-benzimidazole, 4.2 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone was stirred and refluxed for 30 minutes using a water separator. 5.2 Parts of 1-(3-chloropropoxy)-4-fluorobenzene were added at reflux temperature and stirring was continued for 3 hours at this temperature using a water separator. After cooling to room temperature, the salts were filtered off and the filtrate was washed twice with water, dried, filtered and evaporated. The residue was converted into the ethanedioate salt in 2-propanone. The salt was filtered off, washed with 2-propanone and crystallized from methanol. The product was filtered off and dried in vacuo at 80° C., yielding 7 parts (53%) of 2-[[1-[3-(4-fluorophenoxy)propyl]-4-piperidinyl]methyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazole ethanedioate (1:2); mp. 186.7° C. (119).

Workup

  1. temperaturerefluxed for 30 minutes
  2. temperatureat reflux temperature
  3. stirringstirring
  4. filtrationthe salts were filtered off
  5. washthe filtrate was washed twice with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. filtrationThe salt was filtered off
  10. washwashed with 2-propanone
  11. customcrystallized from methanol
  12. filtrationThe product was filtered off
  13. customdried in vacuo at 80° C.

Sources & evidence

ORD record
ord-ee2e4e81a8ea4292b2fc6d084f27a2c0
Source dataset
uspto-grants-1987_09
Patent number
US04695575

Reaction notes

Loading…