Potassium Iodide → HCID 19992260, compound

HRID 345477Notes

Reaction equation

HRID 345477 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.Cl[CH2:24][CH2:25][C:26]([NH:28][CH3:29])=[O:27].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([OH:9])[CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][C:26]([NH:28][CH3:29])=[O:27])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 2493783-chloro-n-methylpropanamideHCID 11208889Bis(4-fluorophenyl)(piperidin-4-yl)methanol

Product 1

HCID 19992260HCID 19992260, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5.0 g (0.017 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 3.0 g (0.025 mole) of 3-chloro-N-methylpropanamide, 15.0 g (0.142 mole) of anhydrous sodium carbonate and 0.3 g (0.002 mole) of potassium iodide in 100 ml of N,N-dimethylformamide was heated on a steam bath for 16 h. The mixture was poured into 1.5 L of water and extracted twice with 150 ml portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 150 g of silica gel on a 60 cm×3.5 cm column, eluted with 10% methanol in methylene chloride. The fractions containing the desired product were partitioned between 15% sodium hydroxide and methylene chloride. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. Upon trituration with petroleum ether (30°-60° C.), the glass solidified. The solid was recrystallized from ethyl acetate/petroleum ether (30°-60° C.) to yield 3.2 g (50%) of white solid, mp 127°-129° C.

Workup

  1. temperaturewas heated on a steam bath for 16 h
  2. extractionextracted twice with 150 ml portions of ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give a dark oil
  7. customThe oil was purified by column chromatography
  8. washeluted with 10% methanol in methylene chloride
  9. additionThe fractions containing the desired product
  10. customwere partitioned between 15% sodium hydroxide and methylene chloride
  11. washThe methylene chloride layer was washed with water and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated under reduced pressure
  14. customto give a glass
  15. customThe solid was recrystallized from ethyl acetate/petroleum ether (30°-60° C.)

Sources & evidence

ORD record
ord-54f85c6841b14e1abfe8faab6cf39ffe
Source dataset
uspto-grants-1991_10
Patent number
US05057524

Reaction notes

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