Benzyl Chloride → HCID 19020637, compound

HRID 1109456Notes

Reaction equation

HRID 1109456 reaction equation
[H-].[Na+].[C:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[NH:13][N:14]=[C:15]3[C:20]=2[CH:19]=[CH:18][C:17]([F:21])=[CH:16]3)[CH2:8][CH2:7]1)(=[O:5])[CH3:4].Cl[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CS(C)=O>[C:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[N:13]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:14]=[C:15]3[C:20]=2[CH:19]=[CH:18][C:17]([F:21])=[CH:16]3)[CH2:8][CH2:7]1)(=[O:5])[CH3:4]

Participants

5

Reactant 3

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 14032627HCID 14032627, compound

Product 1

HCID 19020637HCID 19020637, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred mixture of 15.8 parts of a sodium hydride dispersion 50% and 660 parts of dimethyl sulfoxide were added portionwise 78.4 parts of 1-acetyl-4-(6-fluoro-2H-indazol-3-yl)piperidine under nitrogen atmosphere. Upon complete addition, stirring was continued for 1 hour at room temperature. 42 Parts of chloromethylbenzene were added dropwise during 45 minutes. Upon completion, stirring was continued overnight at room temperature. The reaction mixture was poured into crushed ice and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography (HPLC) over silica gel using a mixture of methylbenzene and methanol (90:10 by volume) as eluent. The first fraction was collected and the eluent was evaporated, yielding 91 parts (86.3%) of 1-acetyl-4-[6-fluoro-2-(phenylmethyl)-2H-indazol-3-yl]piperidine as a residue (int. 1). b) A mixture of 8 parts of 1-acetyl-4-[6-fluoro-2-(phenylmethyl)-2H-indazol-3-yl] piperdine and 70 parts of a hydrochloric acid solution 6N was stirred for 6 hours at reflux temperature. The reaction mixture was evaporated and the oily residue was crystallized from 2-propanol. The product was filtered off and dried, yielding 2 parts (25.1%) of 6-fluoro-2-(phenylmethyl)-3-(4-piperidinyl)-2H-indazole monohydrochloride; mp.>300° C. (int. 2).

Workup

  1. additionUpon complete addition
  2. stirringUpon completion, stirring
  3. waitwas continued overnight at room temperature
  4. additionThe reaction mixture was poured
  5. custominto crushed ice
  6. extractionthe product was extracted with dichloromethane
  7. customThe extract was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography (HPLC) over silica gel using
  11. additiona mixture of methylbenzene and methanol (90:10 by volume) as eluent
  12. customThe first fraction was collected
  13. customthe eluent was evaporated

Sources & evidence

ORD record
ord-92f7235064ca4bef994e90f3de3fcbcd
Source dataset
uspto-grants-1994_06
Patent number
US05321028

Reaction notes

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