Hydrochloric Acid → HCID 19992254, compound

HRID 345491Notes

Reaction equation

HRID 345491 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:23][CH2:24][CH2:25][CH2:26][C:27]([N:29]([CH3:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].Cl>CN(C)C=O.O>[OH2:9].[ClH:23].[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][CH2:26][C:27]([N:29]([CH3:36])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 11208889Bis(4-fluorophenyl)(piperidin-4-yl)methanolHCID 16780864HCID 16780864, compound

Product 1

HCID 19992254HCID 19992254, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 6.4 g (0.030 mole) of 4-chloro-N-methyl-N-phenylbutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 72 h. The mixture was poured into 1.5 L of water and extracted thrice with 250 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 250 g of silica gel on a 65 cm×4 cm column eluted with 5% methanol in methylene chloride. The fractions containing the desired product were combined and concentrated under reduced pressure to give a glass. The glass was converted to the hydrochloric acid salt, and the solid was recrystallized from 2-propanol/isopropyl ether to yield 2.8 g (27%) of the title compound as a white solid, mp 107°-110° C.

Workup

  1. extractionextracted thrice with 250 mL portions of ethyl acetate
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customto give a dark oil
  6. customThe oil was purified by column chromatography
  7. washeluted with 5% methanol in methylene chloride
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated under reduced pressure
  10. customto give a glass
  11. customthe solid was recrystallized from 2-propanol/isopropyl ether

Sources & evidence

ORD record
ord-f30f708a7be84de88fbe93903acf8f7b
Source dataset
uspto-grants-1991_10
Patent number
US05057524

Reaction notes

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