Potassium Fluoride → HCID 19040910, compound

HRID 866064Notes

Reaction equation

HRID 866064 reaction equation
Cl.[F:2][C:3]([F:31])([F:30])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=2)([OH:18])[CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:7][CH:6]=1.[CH2:32]([O:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Cl)=[CH:38][CH:37]=1)[C:33]#[CH:34].[F-].[K+]>>[CH2:32]([O:35][C:36]1[CH:37]=[CH:38][C:39]([CH2:42][N:15]2[CH2:16][CH2:17][CH:12]([C:11]([C:8]3[CH:7]=[CH:6][C:5]([O:4][C:3]([F:30])([F:2])[F:31])=[CH:10][CH:9]=3)([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:27])[F:28])=[CH:21][CH:20]=3)[OH:18])[CH2:13][CH2:14]2)=[CH:40][CH:41]=1)[C:33]#[CH:34]

Participants

4

Reactant 3

HCID 522689Potassium FluorideHCID 107498961-(Chloromethyl)-4-(2-propyn-1-yloxy)benzeneHCID 19040925HCID 19040925, compound

Product 1

HCID 19040910HCID 19040910, compoundYield 64.7%

Procedure

A stirred mixture of 0.8 gram (0.0016 mole) of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine hydrochloride, 0.3 gram (0.0016 mole) of 4-(2-propyn-1-yloxy)phenylmethyl chloride and 0.5 gram (0.0079 mole) of potassium fluoride on Celite® filter aid in 50 mL of acetonitrile was heated at reflux for about 1.3 hours. After this time 0.5 mL (excess) of triethylamine was added, and the reaction mixture became homogeneous. Upon completion of addition, the reaction mixture was heated at reflux for an additional 18 hours. After this time the reaction mixture was cooled, filtered, and the filtrate concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with mixtures of 10-70% diethyl ether in hexane as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 0.6 gram of N-[4-(2-propyn-1-yloxy)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure.

Workup

  1. filtrationfilter aid in 50 mL of acetonitrile
  2. temperaturewas heated
  3. temperatureat reflux for about 1.3 hours
  4. additionAfter this time 0.5 mL (excess) of triethylamine was added
  5. additionUpon completion of addition
  6. temperaturethe reaction mixture was heated
  7. temperatureat reflux for an additional 18 hours
  8. temperatureAfter this time the reaction mixture was cooled
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated under reduced pressure to a residue, which
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-48c6bc513ac24ca9bae7ff516346122f
Source dataset
uspto-grants-1996_10
Patent number
US05569664

Reaction notes

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