Ammonium Chloride → alpha-(4-Fluorophenyl)-alpha-(1-methyl-4-piperidinyl)-3-pyridinemethanol

HRID 484720

Reaction equation

HRID 484720 reaction equation
Cl[CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[Mg].[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)=[O:18])=[CH:13][CH:12]=1.[Cl-].[NH4+]>CC1C=CC=CC=1.O1CCCC1>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]([CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)([C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[OH:18])=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 793424-chloro-N-methylpiperidineHCID 762660(4-Fluorophenyl)(pyridin-3-yl)methanoneHCID 5462224Magnesium

Product 1

HCID 23326054alpha-(4-Fluorophenyl)-alpha-(1-methyl-4-piperidinyl)-3-pyridinemethanolYield 95%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred and cooled Grignard-complex previously prepared starting from a mixture of 134 parts of 4-chloro-1-methylpiperidine, 25 parts of magnesium and 652.5 parts of tetrahydrofuran was added dropwise a solution of 170 parts of (4-fluorophenyl)(3-pyridinyl)methanone in 405 parts of tetrahydrofuran at a temperature between 10°-20° C. Upon completion, stirring was continued for 1 hour at room temperature and for 30 minutes at minutes at reflux. After cooling, the whole was decomposed by pouring onto a mixture of crushed ice and ammonium chloride. 270 Parts of methylbenzene were added. The organic layer was separated, dried, filtered and evaporated. The residue was boiled in acetonitrile with activated charcoal. The latter was filtered off over Hyflo and the filtrate was evaporated, yielding 240 parts (95%) of α-(4-fluorophenyl)-α-(1-methyl-4-piperidinyl)-3-pyridinemethanol as a residue (intermediate 18).

Workup

  1. temperaturecooled Grignard-complex
  2. custompreviously prepared
  3. stirringUpon completion, stirring
  4. temperatureat reflux
  5. temperatureAfter cooling
  6. customThe organic layer was separated
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. filtrationThe latter was filtered off over Hyflo
  11. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-988787aae3214f9d8feb0622a1f04858
Source dataset
uspto-grants-1985_08
Patent number
US04533665

Linked notes

Loading…