Potassium Fluoride → HCID 57261037, compound

HRID 1609115Notes

Reaction equation

HRID 1609115 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17]([N:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]5[C:27](F)=[N:28][CH:29]=[CH:30][CH:31]=5)[CH2:21][CH2:20]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.[F-].[K+].[CH3:35][O-:36].[Na+]>CO>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17]([N:19]4[CH2:24][CH2:23][CH:22]([CH2:25][C:26]5[C:27]([O:36][CH3:35])=[N:28][CH:29]=[CH:30][CH:31]=5)[CH2:21][CH2:20]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 522689Potassium Fluoride2×HCID 10942334Sodium Methoxide2×HCID 22852191HCID 22852191, compound

Product 1

HCID 57261037HCID 57261037, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 1-((9S,10S)-2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylcarbonyl)-4-(2-fluoro-3-pyridylmethyl)piperidine, (2.60 g, 5.8 mmol), prepared as described in Example 55a, in methanol (25 mL) was added potassium fluoride (4.15 g, 71.4 mmol) which caused a slight exotherm (~35° C.). Sodium methoxide solution in methanol (4.4 mL of a 25 wt % solution) was added which caused another exotherm (~50° C.) and thinned the suspension. This suspension was heated to reflux for 6 h. Additional potassium fluoride (4.15 g, 71.4 mmol) was added and the suspension was refluxed for 18 h. Additional sodium methoxide solution (1.0 mL) was added and the suspension was refluxed for 5 h. The mixture was cooled to room temperature, partitioned between basic brine and dichloromethane. The organic extract was separated and the aqueous was extracted with dichloromethane (2X). The dichloromethane extracts were combined, dried over sodium sulfate, filtered and concentrated on a rotary evaporator. The crude foam was purified by flash chromatography on silica (eluant: 15% acetone/hexanes) to give the title compound as a white solid (1.82 g, 3.95 mmol, 68%).

Workup

  1. customa slight exotherm (~35° C.)
  2. customanother exotherm (~50° C.)
  3. temperatureThis suspension was heated
  4. temperatureto reflux for 6 h
  5. temperaturethe suspension was refluxed for 18 h
  6. temperaturethe suspension was refluxed for 5 h
  7. custompartitioned between basic brine and dichloromethane
  8. extractionThe organic extract
  9. customwas separated
  10. extractionthe aqueous was extracted with dichloromethane (2X)
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated on a rotary evaporator
  14. customThe crude foam was purified by flash chromatography on silica (eluant: 15% acetone/hexanes)

Sources & evidence

ORD record
ord-f456b8ae3cb74ca9b6c83a4992be05dc
Source dataset
uspto-grants-1995_03
Patent number
US05399568

Reaction notes

Loading…