Methyl Isobutyl Ketone → HCID 88670912, compound

HRID 1904867Notes

Reaction equation

HRID 1904867 reaction equation
Br[CH2:2][CH2:3][S:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:22]=3[N:21]=[C:20]2[CH2:29][CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[OH2:28].[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:22]=3[N:21]=[C:20]2[CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:2][CH2:3][S:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:32][CH2:31]2)=[CH:16][CH:17]=1.[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][N:19]2[C:23]3[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:22]=3[N:21]=[C:20]2[CH2:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:2][CH2:3][S:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:32][CH2:31]2)=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 78553((2-Bromoethyl)thio)benzeneHCID 14012880HCID 14012880, compound

Product 1

HCID 88670912HCID 88670912, compoundYield 27.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 6.48 parts of [(2-bromoethyl)thio]benzene, 6.8 parts of 1-[(4-fluorophenyl)methyl]-2-(4-piperidinylmethyl)-1H-benzimidazol-5-ol, 4.2 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone was stirred for 2 hours at reflux temperature using a water separator. After cooling to room temperature, the reaction mixture was poured into water. The layers were separated. The organic layer was washed with 500 parts of water, dried, filtered and evaporated. The residue was taken up in a mixture of trichloromethane and methanol (95:5 by volume) and 25 parts of silica gel. After stirring for 15 minutes, the whole was filtered, washed with the eluent and the filtrate was evaporated. The residue was boiled in 160 parts of 2-propanone. The mixture was stirred overnight at room temperature. The product was filtered off, washed with 2-propanone and crystallized from 280 parts of 2-propanone. The product was filtered off, washed with 2-propanone and dried in vacuo at 50° C., yielding 2.7 parts (27.8%) of 1-[(4-fluorophenyl)methyl]-2-[[1-[2-(phenylthio)ethyl]-4-piperidinyl]methyl]-1-H-benzimidazol-5-ol hemihydrate; mp. 193.8° C. (570).

Workup

  1. temperatureat reflux temperature
  2. customThe layers were separated
  3. washThe organic layer was washed with 500 parts of water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. additionThe residue was taken up in a mixture of trichloromethane and methanol (95:5 by volume) and 25 parts of silica gel
  8. stirringAfter stirring for 15 minutes
  9. filtrationthe whole was filtered
  10. washwashed with the eluent
  11. customthe filtrate was evaporated
  12. stirringThe mixture was stirred overnight at room temperature
  13. filtrationThe product was filtered off
  14. washwashed with 2-propanone
  15. customcrystallized from 280 parts of 2-propanone
  16. filtrationThe product was filtered off
  17. washwashed with 2-propanone
  18. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-4f75c793d2ed44fa87eb797a52557f5d
Source dataset
uspto-grants-1989_06
Patent number
US04839374

Reaction notes

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