Ethylene Oxide → 4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol

HRID 477658Notes

Reaction equation

[O:1]1[CH2:3][CH2:2]1.[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[NH:21][CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:7][CH:6]=1>CO>[F:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[N:14]=[C:13]2[NH:21][CH:22]2[CH2:23][CH2:24][N:25]([CH2:3][CH2:2][OH:1])[CH2:26][CH2:27]2)=[CH:7][CH:6]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 9 parts of oxirane, 3.24 parts of 1-(4-fluorophenylmethyl)-N-(4-piperidinyl)-1H-benzimidazol-2-amine and 400 parts of methanol was stirred first overnight at room temperature and further for 4 hours at 50° C. The reaction mixture was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 4-methyl-2-pentanone and 2,2'-oxybispropane, yielding 15 parts of 4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol; mp. 138.7° C. (intermediate 93).

Workup

customThe reaction mixture was evaporated
customThe residue was purified by column-chromatography over silica gel using
additiona mixture of trichloromethane and methanol
customThe pure fractions were collected
customthe eluent was evaporated
customThe residue was crystallized from a mixture of 4-methyl-2-pentanone and 2,2'-oxybispropane

Sources & evidence

ORD record: ord-33fa2211ccb34ac985882a722c9a52b9
Source dataset: uspto-grants-1989_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04888426

Reaction notes

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