Benzene, 1-(chloromethyl)-2-fluoro- → HCID 14013089, compound

HRID 1904866Notes

Reaction equation

HRID 1904866 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18]3[NH:22][C:21]4[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=4[N:19]=3)[CH2:13][CH2:12]2)=[CH:5][CH:4]=1.CN(C)C(=O)C.[H-].[Na+].Cl[CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[F:43]>O>[F:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][N:22]1[C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[N:19]=[C:18]1[CH2:17][CH:14]1[CH2:15][CH2:16][N:11]([CH2:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 24758Sodium hydrideHCID 31374Dimethylacetamide2×HCID 14518076HCID 14518076, compound

Product 1

HCID 14013089HCID 14013089, compoundYield 65.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred mixture of 3.5 parts of 2-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]methyl]-1H-benzimidazole and 18 parts of N,N-dimethylacetamide were added portionwise 0.5 parts of a sodium hydride dispersion 59.4% at room temperature. After stirring for 35 minutes at room temperature and for 10 minutes at 60° C., a solution of 1.7 parts of 1-(chloromethyl)-2-fluorobenzene in 9 parts of N,N-dimethylacetamide was added dropwise at 60° C. After stirring for 10 minutes, the reaction mixture was cooled and poured into 150 parts of water. The product was extracted twice with 4-methyl-2-pentanone. The combined extracts were washed with water, dried, filtered and evaporated. The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanone. The product was filtered off and dried, yielding 3.0 parts (65.5%) of 1-[(2-fluorophenyl)methyl]-2-[[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-methyl]-1H-benzimidazole; mp. 109.3° C. (515).

Workup

  1. stirringAfter stirring for 10 minutes
  2. temperaturethe reaction mixture was cooled
  3. extractionThe product was extracted twice with 4-methyl-2-pentanone
  4. washThe combined extracts were washed with water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanone
  9. filtrationThe product was filtered off
  10. customdried

Sources & evidence

ORD record
ord-81d60237b5364c94a638fe06eb7fd8f1
Source dataset
uspto-grants-1989_06
Patent number
US04839374

Reaction notes

Loading…