Acetonitrile → 4-(4-Fluorobenzoyl)-alpha-methyl-1-piperidineacetonitrile

HRID 1156318Notes

Reaction equation

HRID 1156318 reaction equation
Cl[CH:2]([CH3:5])[C:3]#[N:4].Cl.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[O:15])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>O>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([CH:16]2[CH2:21][CH2:20][N:19]([CH:2]([CH3:5])[C:3]#[N:4])[CH2:18][CH2:17]2)=[O:15])=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 5192252-ChloropropionitrileHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochloride

Product 1

HCID 134765514-(4-Fluorobenzoyl)-alpha-methyl-1-piperidineacetonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 25 parts of 2-chloropropanenitrile, 61 parts of (4-fluorophenyl)(4-piperidinyl)methanone hydrochloride, 63 parts of sodium carbonate and 160 parts of acetonitrile is stirred and refluxed (100° C.) overnight. The reaction mixture is cooled, water is added and the layers are separated. The aqueous phase is extracted with 4-methyl-2-pentanone. The combined organic phases are dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane, hexane and methanol (50:49:1 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The solid residue is crystallized from 2,2'-oxybispropane. The product is filtered off, and dried yielding 17 parts of 4-(4-fluorobenzoyl)-α-methyl-1-piperidineacetonitrile; mp. 126.7° C.

Workup

  1. temperatureThe reaction mixture is cooled
  2. customthe layers are separated
  3. extractionThe aqueous phase is extracted with 4-methyl-2-pentanone
  4. customThe combined organic phases are dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane, hexane and methanol (50:49:1 by volume) as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. customThe solid residue is crystallized from 2,2'-oxybispropane
  12. filtrationThe product is filtered off
  13. customdried

Sources & evidence

ORD record
ord-05342ea46e2640429fc439a4534acacb
Source dataset
uspto-grants-1982_06
Patent number
US04335127

Reaction notes

Loading…